Microvascular Research[JOURNAL]
Sun
200 papers
Harnessing exosomal mediators for advanced wound healing: Mechanisms and therapeutic potential in angiogenesis.
Saadh MJ, Allela OQB, Kareem RA … +9 more , Baldaniya L, Roopashree R, Thakur V, Kaur M, Valiev A, Sameer HN, Yaseen A, Athab ZH, Adil M
Microvasc Res · 2025 Nov · PMID 40848894 · Publisher ↗
Angiogenesis is critical for effective wound healing, supplying oxygen and nutrients to regenerating tissues. In chronic conditions like diabetes, impaired angiogenesis leads to delayed healing, chronic wounds, and signi...
Angiogenesis is critical for effective wound healing, supplying oxygen and nutrients to regenerating tissues. In chronic conditions like diabetes, impaired angiogenesis leads to delayed healing, chronic wounds, and significant healthcare burdens. Exosomes, nano-sized extracellular vesicles derived from cells such as mesenchymal stem cells (MSCs), amniotic epithelial cells, and keratinocytes, have emerged as key mediators in promoting angiogenesis. Laden with bioactive cargos-including microRNAs, proteins, and lipids-exosomes orchestrate endothelial cell proliferation, migration, and extracellular matrix remodeling to enhance vascularization. This review explores the molecular mechanisms by which exosomes drive angiogenesis, highlighting their role in modulating signaling pathways and immune responses critical for tissue repair. We evaluate the therapeutic promise of exosome-based delivery systems, integrating insights from biological, pharmaceutical, and cell-based approaches. By leveraging these advancements, exosomal therapies offer transformative potential for managing chronic wounds and ischemic conditions, paving the way for innovative regenerative medicine strategies.
Pilot study on near-infrared spectroscopy in peripheral artery disease: Differentiating upper and lower limbs and its correlation with the ankle-brachial index.
Braga Amorim J, Dias Neto M, Magalhães S … +1 more , S Barros A
Microvasc Res · 2025 Nov · PMID 40848893 · Publisher ↗
Peripheral artery disease (PAD) is a global health challenge, with current diagnostic methods, including the ankle-brachial index (ABI), having limitations, particularly in patients with arterial calcification. Near-infr...
Peripheral artery disease (PAD) is a global health challenge, with current diagnostic methods, including the ankle-brachial index (ABI), having limitations, particularly in patients with arterial calcification. Near-infrared spectroscopy (NIRS) offers potential advantages as a non-invasive assessment tool, yet its clinical utility in PAD remains underexplored. This pilot study evaluated NIRS for differentiating between non-ischemic upper limbs and ischemic lower limbs, and assessed NIRS correlation with ABI. To do that, we performed an observational, cross-sectional study employing a convenience sample of 51 patients with PAD attending the vascular surgery outpatient clinic. A portable spectrometer recorded NIRS measurements from the right thumb and both halluces at rest. Random Forest classification was implemented to differentiate upper and lower limbs, revealing distinct NIRS patterns between upper and lower limbs, with an area under the ROC curve of 0.91 (95 % CI 0.88-0.94). Interval Partial Least Squares regression (iPLS) identified wavelength regions correlating with ABI, with the 1429-1463 nm interval being the most informative for ABI prediction, with a modest correlation (R = 0.167, RMSECV = 0.186). NIRS demonstrated strong discriminative capability between non-ischemic upper and ischemic lower limbs in PAD. While the correlation between NIRS and ABI was modest, it suggests potential clinical relevance. These findings indicate that NIRS could be a rapid, portable, non-invasive complementary tool for PAD assessment.
Prognostic value of the wall-to-lumen ratio of retinal arteries in patients with end-stage chronic kidney disease.
Faure C, Castrale C, Benabed A … +3 more , Lezé R, Cognard P, Paques M
Microvasc Res · 2025 Nov · PMID 40846134 · Publisher ↗
PURPOSE: To investigate the hypothesis that the wall-to-lumen ratio (WLR) of retinal arteries is predictive of morbidity and mortality in patients with end-stage chronic kidney disease (CKD). METHODS: Prospective single...
PURPOSE: To investigate the hypothesis that the wall-to-lumen ratio (WLR) of retinal arteries is predictive of morbidity and mortality in patients with end-stage chronic kidney disease (CKD). METHODS: Prospective single center clinical study. In 83 patients with CKD (average age (±SD) 75.8 (±11.4) years), arterial metrics in the retinal vasculature were measured using adaptive optics ophthalmoscopy (AOO; rtx1, ImagineEyes, France). Multivariate analysis including vascular metrics and biological parameters was done to identify predictive risk factors of the morbidity and mortality rates at 3 years. RESULTS: At inclusion, the mean (±SD) wall-to-lumen ratio (WLR) was 0,34 (± 0,17). No correlation was found between blood pressure and the WLR. The 1, 2 and 3-year survival rates were 74.7 %, 57.3 % and 42.1 %, respectively. The 1, 2 and 3-year rates of nonfatal cardiovascular events were 25.3 %, 42.7 % and 56.5 %, respectively. Four patients were lost to follow-up. Based on a Cox model, the cumulative 3-year relative risk of death or cardiovascular event was inversely correlated to the initial WLR (RR 2.5 if WLR <0.36, 2.1 if <0.3, 4.9 if <0.27), age over 80 years (RR 1.9), and sedentarity (RR 2.3). Metabolic factors were not predictive of event-free survival. CONCLUSIONS: In patients with end-stage CKD, a lower WLR is associated with a higher morbidity and mortality rate at 3 years. Retinal vascular metrics may therefore provide novel biomarkers for the prediction of event-free survival in CKD. Additional studies are necessary to elucidate the underlying relationship.
Key contributors to cell-free layer formation: An experimental investigation of hematocrit and shear rate gradient.
Salame M, Fenech M
Microvasc Res · 2025 Nov · PMID 40846133 · Publisher ↗
The formation of the cell-free layer (CFL) near vessel walls plays a critical role in microcirculatory function, influencing blood rheology, oxygen delivery, and endothelial interactions. While hematocrit (Ht) is a well-...
The formation of the cell-free layer (CFL) near vessel walls plays a critical role in microcirculatory function, influencing blood rheology, oxygen delivery, and endothelial interactions. While hematocrit (Ht) is a well-established determinant of CFL thickness, the influence of shear-related parameters remains debated due to conflicting findings in the literature. In this study, we systematically quantified the optical CFL thickness (δ) in circular glass microchannels (25-50 μm diameter) under varying hematocrit levels (5-20 %), flow rates, and suspension media (phosphate-buffered saline and plasma). High-resolution microfluidic imaging and micro-particle image velocimetry (μPIV) were used to extract local velocity fields and calculate shear rate gradients (∇γ̇). Rather than treating ∇γ̇ as an imposed variable, we characterize it as a flow-derived descriptor of the local hydrodynamic environment. Across conditions, ∇γ̇ showed stronger correlations with CFL thickness than bulk shear rate. In PBS, increasing ∇γ̇ was associated with reduced CFL thickness, likely due to enhanced shear-induced dispersion. In contrast, in plasma, higher ∇γ̇ values promoted disaggregation of red blood cell (RBC) aggregates and restored hydrodynamic lift, resulting in thicker CFLs. These trends underscore the importance of considering both the suspension medium and spatial shear variations when interpreting RBC behavior. Comparison with prior in vitro, in vivo, and computational studies suggests that discrepancies in reported CFL trends can often be reconciled by accounting for differences in aggregation potential and local shear rate gradients. This work provides a unified experimental framework for interpreting CFL dynamics and highlights ∇γ̇ as a valuable parameter for describing flow-mediated RBC redistribution in the microcirculation.
Assessing coronary microvascular dysfunction in refractory no-reflow: Insights from dynamic myocardial perfusion scintigraphy and cardiac MRI.
Dil S, Ryabov V, Maslov L … +5 more , Mochula O, Mochula A, Kercheva M, Zavadovsky K, Vyshlov E
Microvasc Res · 2025 Nov · PMID 40846132 · Publisher ↗
BACKGROUND: Refractory no-reflow correlates with worse outcomes, including larger infarct sizes, impaired ventricular function, and higher mortality rates, despite advances in percutaneous coronary intervention (PCI). Mi...
BACKGROUND: Refractory no-reflow correlates with worse outcomes, including larger infarct sizes, impaired ventricular function, and higher mortality rates, despite advances in percutaneous coronary intervention (PCI). Microvascular obstruction (MVO) and increased left ventricular end-diastolic pressure (LVEDP) are implicated in the pathogenesis, potentially exacerbating ischemic injury and limiting myocardial recovery. While pressure-wire-derived indices such as the Index of Microcirculatory Resistance (IMR) have been validated against MRI-defined MVO in STEMI populations, their invasive nature and procedural complexity limit broad adoption. In contrast, combining dynamic SPECT and cardiac MRI enables a comprehensive non-invasive functional-structural evaluation of coronary microvascular function in refractory no-reflow. METHODS: This study is a post hoc analysis of a larger randomized controlled trial (RCT) evaluating the efficacy and safety of intracoronary epinephrine in patients with refractory no-reflow post-PCI (ClinicalTrials.govNCT04573751). We evaluated global coronary flow metrics (RMBF, SMBF, gRFI) derived from SPECT and assessed structural markers of microvascular injury (infarct size, MVO) on MRI. Echocardiographic estimations of LVEDP were also analyzed. RESULTS: Dynamic SPECT revealed suboptimal stress myocardial blood flow in most patients, highlighting microvascular impairment. Elevated estimated LVEDP was significantly correlated with indexed MVO (rs = 0.678, p = 0.001). Traditional flow reserve metrics showed limited sensitivity, whereas global relative flow increase (gRFI) showed a statistically significant correlation with MVO, highlighting its added value in detecting stress-induced perfusion abnormalities. Given the small sample and potential outlier influence, this observation should be considered hypothesis-generating. CONCLUSION: Our findings support that functional impairments-particularly elevated LVEDP and reduced gRFI-are associated with refractory no-reflow. In particular, gRFI may serve as a promising non-invasive marker of microvascular dysfunction, complementing structural imaging. None-theless, further validation in larger cohorts is needed. This study advocates for refined multimodal imaging strategies and tailored therapeutic approaches targeting dynamic microvascular disturbances to improve outcomes in refractory no-reflow.
Retinal blood flow in eyes with primary open-angle glaucoma using a new Adaptive Optics Laser Doppler Velocimeter device.
Altuwaym O, Geiser M, Mautuit T … +2 more , Truffer F, Chiquet C
Microvasc Res · 2025 Nov · PMID 40825524 · Publisher ↗
PURPOSE: To measure retinal blood flow (RBF) in the retinal veins of patients with primary open-angle glaucoma (POAG) and to compare it with healthy controls. A secondary objective was to determine any correlation betwee...
PURPOSE: To measure retinal blood flow (RBF) in the retinal veins of patients with primary open-angle glaucoma (POAG) and to compare it with healthy controls. A secondary objective was to determine any correlation between RBF and visual field (VF) loss or retinal nerve-fiber layer (RNFL) thickness. METHOD: Twelve patients with POAG and 11 healthy controls were included in a prospective single-center study. Our prototype Adaptive Optics Laser Doppler Velocimeter (AO-LDV) consisted of a laser Doppler velocimeter combined with an adaptive optic fundus camera (rtx1, Imagine Eyes®) allowing measurement of blood vessel diameter and therefore, calculation of blood flow within the vessel. Blood flow in the superior temporal vein (STV) was compared with that in the inferior temporal vein (ITV). All subjects underwent eye examinations including visual field (Humphrey 24-2 SITA-standard strategy) and measurement of retinal nerve-fiber layer (RNFL) thickness using a Cirrus HD-OCT (optic disc 200 × 200 cube) protocol. Sectoral structure-function relationships were studied in the glaucoma group. RESULTS: The velocity in the STV was lower in the glaucoma group (6.30 ± 1.6 mm/s) compared to the control group (8.6 ± 2.8 mm/s, p = 0.07), with no significant differences in the ITV. There were no significant differences in STV or ITV diameters between the groups. We found no relationship between either STV or ITV retinal blood flow and visual field or RNFL thickness. CONCLUSION: Our prototype AO-LDV allowed accurate measurement of RBF in patients with glaucoma and showed that RBF was not reduced in the early or moderate stages of glaucoma. These preliminary results should be confirmed in a larger study, especially in late-stage glaucoma.
Intermittent heat stress facilitates the autophagy and apoptosis of the vascular endothelium in spontaneously hypertensive rats via the AMPK/mTOR/ULK1 pathway.
Yang C, Zhao H, Wu X … +4 more , Tuo W, Hou L, Chai D, Li G
Microvasc Res · 2025 Nov · PMID 40784609 · Publisher ↗
This study examined the autophagy and apoptosis of vascular endothelial cells in spontaneously hypertensive rats (SHRs) under intermittent heat stress and determined whether the AMP-activated protein kinase (AMPK)/mammal...
This study examined the autophagy and apoptosis of vascular endothelial cells in spontaneously hypertensive rats (SHRs) under intermittent heat stress and determined whether the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/Unc-51 like autophagy activating kinase (ULK1) pathway is involved in autophagy regulation. Wistar-Kyoto (WKY) rats were assigned to control (WKY-CN), intermittent heat stress (WKY-8), and continuous heat stress (WKY-24) groups. SHRs were also assigned to three groups: SHR-CN, SHR-8, and SHR-24. Western blotting assay, immunohistochemical assay, and immunofluorescence assay were performed for observing expression of proteins related to autophagy and apoptosis and the AMPK/mTOR/ULK1 pathway. Vascular endothelial cells underwent autophagy and apoptosis following heat stress, as revealed by high expression of autophagy- and apoptosis-related proteins. Heat stress elevated AMPK and ULK1 expression levels, whereas it decreased mTOR phosphorylation in SHR-8 and SHR-24 groups. Finally, the rats in SHR-8 group were administered an autophagy inducer (rapamycin, Rapa) and inhibitor (3-Methyladenine, 3-MA), respectively, for evaluating autophagy induction and inhibition. Following Rapa administration, LC3-II/LC3-I and Caspase-3 expression levels were elevated in the intermittent heat stress groups as compared to those in the control groups; in contrast, 3-MA attenuated cell death in the intermittent heat stress groups. Overall, this study demonstrated that intermittent heat stress elicits autophagy and apoptosis processes in vascular endothelial cells and that the AMPK/mTOR/ULK1 pathway participates in regulating autophagy and apoptosis.
RAS-RH up-regulates the level of miR-126 and inhibits the opening of mPTP in a rat model of coronary microvascular disease.
Jiang H, Wang R, Liu A … +7 more , Liu J, Wang X, Lin W, Ren C, Liu K, Zhao X, Li Y
Microvasc Res · 2025 Nov · PMID 40774633 · Publisher ↗
BACKGROUND: Coronary microvascular dysfunction (CMVD) significantly impairs cardiac function and worsens prognosis in patients with cardiovascular diseases, yet no definitively effective pharmacological treatment current...
BACKGROUND: Coronary microvascular dysfunction (CMVD) significantly impairs cardiac function and worsens prognosis in patients with cardiovascular diseases, yet no definitively effective pharmacological treatment currently exists. Endothelial cell injury stands as the core pathogenic mechanism of CMVD, however, the molecular mechanisms underlying X-ray radiation-induced endothelial damage remain poorly understood. Although our research group has previously demonstrated that RAS-RH possesses pro-angiogenic properties, its therapeutic potential and mechanistic basis in treating CMVD remain unexplored. Aim This study aims to investigate the potential mechanism by which RAS-RH mitigates radiation-induced coronary microcirculation dysfunction through the inhibition of mitochondrial membrane permeability transition pore (mPTP) opening in endothelial cells. METHODS: We employed a comprehensive set of techniques, including transthoracic echocardiography, coronary microvessel casting technique, carstairs and heidenhain staining, immunohistochemistry, enzyme-linked immunosorbent assay, Western blot, fluorescence in situ hybridization, transmission electron microscopy, TUNEL assay, and flow cytometry, to systematically evaluate cardiac function, coronary vascular structure, myocardial pathological changes, ultrastructural damage, apoptosis, and protein marker expression in an animal model. RESULTS: In the CMVD rat model, X-ray radiation induced cardiac dysfunction, accompanied by elevated levels of vasoactive substances (TXA₂, ET-1, and vWF) and reduced nitric oxide (NO) production. Coronary vascular injury worsened, evidenced by decreased vascular volume, narrowed lumen diameter, and shortened vessel length. Additionally, capillary density was reduced, myocardial ischemia was exacerbated, and intravascular thrombosis was aggravated. At the molecular level, mPTP-related proteins (CypD, VDAC, F₁F₀-ATPase and ANT) exhibited abnormal expression, while apoptosis-related proteins (Cytc, AIF, caspase-9, and caspase-3) were upregulated, leading to increased apoptotic severity. Ultrastructural damage in cardiomyocytes and telocytes was aggravated, and miR-126 expression was downregulated. These findings suggest that X-ray radiation induces CMVD by triggering excessive mPTP opening in endothelial cells. Notably, interventions with RAS-RH, miR-126 agomir and RAS-RH + miR-126 agomir significantly ameliorated these pathological changes to varying degrees. This demonstrates that RAS-RH mitigates X-ray radiation-induced CMVD by upregulating miR-126 to suppress mPTP overactivation. CONCLUSION: RAS-RH effectively ameliorates X-ray radiation-induced CMVD by modulating miR-126 expression to inhibit pathological opening of the mPTP in endothelial cells. This finding provides novel mechanistic evidence supporting RAS-RH as a therapeutic strategy for CMVD.
Comparative analysis of superficial collecting lymph vessels in normal tissue and lymphedema using video-capillaroscopy.
Matsui C, Tsukuura R, Miyazaki T … +7 more , Ishibashi S, Tanaka T, Nishimura T, Arai G, Escandón JM, Mortada H, Yamamoto T
Microvasc Res · 2025 Nov · PMID 40774632 · Publisher ↗
INTRODUCTION: Lymphedema is a chronic, progressive disorder characterized by impaired lymphatic transport, tissue swelling, and fibrosis. This study used video-capillaroscopy, a high-resolution imaging technique, to asse...
INTRODUCTION: Lymphedema is a chronic, progressive disorder characterized by impaired lymphatic transport, tissue swelling, and fibrosis. This study used video-capillaroscopy, a high-resolution imaging technique, to assess superficial collecting lymphatic vessels and their vasa vasorum in patients with lymphedema. By comparing these microvascular structures to those in healthy tissue, we aimed to identify early vascular changes contributing to disease progression. METHODS: VC recordings were retrospectively analyzed from 28 limbs in 17 patients with lower extremity lymphedema and 53 lymphatic vessels in 12 cancer patients undergoing reconstructive surgery. In the latter group, observations were performed on normal subcutaneous tissue exposed at the donor site during flap harvest. These areas showed no tumor involvement, regional metastasis, or prior chemotherapy/radiotherapy. Thus, all normal tissue observations were made on untreated, unaffected sites. VCLs were classified into six stages (0-5) based on morphology and flow. Vessel diameter and red blood cell (RBC) velocity were measured. Statistical significance was set at p < 0.05. RESULTS: In normal donor tissue, mean VCL main vessel diameter and RBC velocity were 0.038 ± 0.031 mm and 185 ± 160.5 μm/s. In lymphedema, these values were reduced to 0.033 ± 0.024 mm and 28.3 ± 36.8 μm/s (p < 0.001). VCL Stage 0 showed preserved flow (p = 0.178), while Stages 1-5 exhibited progressive impairment. CONCLUSION: These findings suggest that early ischemic changes in the vasa vasorum may precede lymphatic dysfunction and fibrosis in lymphedema. Preserving microvascular integrity should be a therapeutic focus, alongside drainage support. Further studies are needed to clarify clinical relevance and optimize treatment strategies.
Influence of pericyte-like vessel dilation on RBC flux in an In Vitro microvascular network.
Bucciarelli A, Obrist D
Microvasc Res · 2025 Nov · PMID 40769421 · Publisher ↗
Efficient oxygen delivery in the brain relies on a finely tuned balance between vascular architecture and dynamic flow regulation. While red blood cells (RBCs) passively flow through the capillary network, neurovascular...
Efficient oxygen delivery in the brain relies on a finely tuned balance between vascular architecture and dynamic flow regulation. While red blood cells (RBCs) passively flow through the capillary network, neurovascular coupling ensures that the blood supply adapts to meet the metabolic demands of active neurons. Pericytes, contractile cells embedded in the capillary walls, play a key role in this process by modulating capillary diameter in response to neural signals. While pericytes are believed to enable rapid and localized blood flow regulation, their contributions in time and space remain debated. This study investigates the effects of pericyte-like vessel dilation (i.e., pericyte relaxation) on RBC distribution and flow dynamics using an in vitro microfluidic model. We investigate how pericyte-induced dynamic cross-sectional changes affect RBC distribution and velocity in a capillary network. By employing a programmable pressure pump to simulate gradual variations in capillary diameter, we observed that short-time dilation increased RBC velocity and hematocrit near the dilation site, enhancing localized perfusion. In contrast, prolonged dilation led to a network-wide RBC redistribution minimizing hydraulic resistance, ultimately depleting hematocrit due to the network Fåhræus effect. These findings highlight the dynamic and adaptive nature of capillary blood flow, where sustained localized changes can propagate into systemic effects over time. More broadly, this study provides new insights into the interplay between localized flow regulation and systemic capillary network dynamics, revealing how geometric and dynamic factors govern RBC behavior and perfusion.
Identification of shear stress as a potential vasoconduction signal across microvascular networks.
Hu NW, Hossain MMN, Withrow J … +6 more , Walker R, Kazempour A, Tsoukias N, Welsh DG, Murfee WL, Balogh P
Microvasc Res · 2025 Nov · PMID 40749748 · Publisher ↗
The objective of this study was to computationally estimate the effects of vessel specific vasoconstriction on immediate shear stress changes across microvascular networks. Shear stress due to microvascular blood flow is...
The objective of this study was to computationally estimate the effects of vessel specific vasoconstriction on immediate shear stress changes across microvascular networks. Shear stress due to microvascular blood flow is an established initiator of ion-mediated signaling along microvessels which regulates control of microcirculatory blood flow. Yet, beyond initiating local vasomotion in a vessel, shear stress as a vasoconduction signal itself and characteristics of hydrodynamic propagation via blood flow are not well understood. In the current work, we use images of mesenteric microvascular networks from adult rat tissues and a network segmental blood flow model to simulate various vessel constriction scenarios and estimate subsequent shear stress changes and distances these changes spread from the site of constriction. Scenarios involving both arteriolar constriction and capillary constriction are considered, in addition to a microvascular network from muscle tissue. The findings generally reveal heterogenous and physiologically relevant shear stress changes across the networks for all cases, with magnitudes spanning a wide range and can exceed 30 dyne/cm. Further, physiological relevant wall shear changes were predicted at distances several mm from the stimulus site. Spatial patterns of shear stress change relative to network topology and capillary density are also identified. Altogether, the results invigorate consideration and discussion about shear stress as a potential player in vasoconduction responses.
PCSK9 inhibitor improved cardiac function after acute myocardial infarction in rats.
An H, Zhu J, Li Q
Microvasc Res · 2025 Nov · PMID 40714004 · Publisher ↗
BACKGROUND: This study investigated the effects and possible mechanisms of Protein expression of protein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab on cardiac function in rats with acute myocardial i...
BACKGROUND: This study investigated the effects and possible mechanisms of Protein expression of protein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab on cardiac function in rats with acute myocardial infarction (AMI). METHODS: The AMI model was established by ligating the left anterior descending coronary artery in rats. The mRNA expression of PCSK9 in myocardial tissues was detected by real-time fluorescent quantitative PCR (RT-qPCR). Echocardiography was used to examine the cardiac function indexes. Hematoxylin-eosin (HE) and Masson stainings were used to detect myocardial pathologic injury. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to detect myocardial infarction area. Serum levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), lactate dehydrogenase (LDH), creatine kinase isoenzymes (CK-MB), cardiac troponin T (cTnT), interleukin-1β (IL-1β), interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) were detected by ELISA. CD31 and vascular endothelial growth factor (VEGF) positive expression was detected by immunohistochemistry. Protein expression levels of PCSK9, Bax, Bcl-2, cleaved-caspase3, receptor interacting protein kinase 1 (RIPK1), RIPK3, mixed lineage kinase domain-like (MLKL), and p-MLKL were detected in myocardial tissues by western blot. RESULTS: The mRNA level and protein expression of PCSK9 were significantly increased in AMI rats. PCSK9 inhibitor evolocumab reduced the levels of LDL-C and TC in serum, thereby improving dyslipidemia. And, evolocumab up-regulated the levels of left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), and down-regulated the levels of left ventricular end systolic diameter (LVESD), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic volume (LVESV), and left ventricular end diastolic volume (LVEDV), which in turn improved cardiac function. In addition, evolocumab attenuated myocardial pathological injury, reduced myocardial infarction area, lowered the levels of LDH, CK-MB, cTnT, IL-1β, IL-17, and TNF-α, and inhibited apoptosis rate, down-regulated Bax, cleaved-caspase3, RIPK1, RIPK3, MLKL, p-MLKL expression, and up-regulated Bcl-2 protein expression, CD31 and VEGF positive expression. CONCLUSION: The PCSK 9 inhibitor evolocumab improved cardiac function in AMI rats, and the mechanism may be related to the RIPK1/RIPK3/MLKL pathway.
Novel in vivo porcine models of chronic ischemic tissue.
Frelichova V, Bem R, Chlupac J … +7 more , Dubsky M, Husakova J, Nemcova A, Voska L, Simunkova Z, Tichanek F, Fronek J
Microvasc Res · 2025 Sep · PMID 40691888 · Publisher ↗
There is a lack of reliable in vivo models that replicate limb-threatening ischemia in humans. To fill this gap, we developed and validated two novel porcine ischemic models: ischemic limb and dorsal flap models, both wi...
There is a lack of reliable in vivo models that replicate limb-threatening ischemia in humans. To fill this gap, we developed and validated two novel porcine ischemic models: ischemic limb and dorsal flap models, both with and without streptozotocin-induced hyperglycemia (N = 3 per group, 12 in total). Hind limb ischemia model was induced via different arterial ligations, with two ischemic and three control wounds per animal. In the flap model, four full-thickness flaps were created on the dorsum with silicone sheets to block reperfusion, and excisional wounds were made on the top. One non-ischemic wound served as control. Transcutaneous oxygen pressure (TcPO), wound area, and microvascular density were measured, with TcPO and wound area assessed longitudinally. Data analysis focused on detailed visualization and Bayesian hierarchical modelling to account for the small sample size. Developed models exhibited stable ischemia and prolonged wound healing, with TcPO remaining under 30 mmHg over 28 days, and wound healing extending beyond two weeks. The flap model showed slower TcPO recovery and greater chronicity compared to the limb model, without reliable effect of hyperglycemia. Thus, the porcine flap model shows the highest potential as a relevant model for chronic limb-threatening ischemia.
Evaluation of neovascularization in murine osteoarthritis using micro-computed tomography.
Talaie R, Torkian P, Spano A … +2 more , Clayton A, Golzarian J
Microvasc Res · 2025 Sep · PMID 40681017 · Publisher ↗
PURPOSE: The study aimed to examine neovascularization in murine osteoarthritis (OA) using micro-computed tomography (μCT). MATERIALS AND METHODS: OA was induced in eighteen mice through intra-articular collagenase injec...
PURPOSE: The study aimed to examine neovascularization in murine osteoarthritis (OA) using micro-computed tomography (μCT). MATERIALS AND METHODS: OA was induced in eighteen mice through intra-articular collagenase injection, designating the left hindlimbs as OA models and the right hindlimbs as controls. Mice were monitored for 4, 8, or 12 weeks post-induction. Hindlimbs underwent overnight tissue fixation and were then subjected to μCT scanning. Quantification of unnamed arterial branches spanned from the femoral artery's terminal branching point to 2.5 mm below the tibial plateau. RESULTS: Baseline characteristics did not differ significantly between control and OA-induced groups (p > 0.05). Collagenase-treated limbs showed a significantly higher number of unnamed arterial branches compared to controls (11.6 vs. 7.5, p < 0.001), reflecting increased neovascularization. This elevation persisted across all post-induction time points, with no significant time-dependent trend (p = 0.09) or interaction between time and treatment group (p = 0.17). Spatial analysis revealed that neovessels were predominantly localized to peri-meniscal (61 %) and subchondral (29 %) regions. CONCLUSION: Collagenase-induced OA in mice results in sustained and spatially patterned neovascularization, detectable using non-contrast μCT. These findings underscore the utility of μCT for tracking vascular remodeling in OA and highlight potential anatomical targets for angiogenesis-modulating therapies.
The electrophysiological effects of angiotensin 1-7 on hypertrophic myocardium in spontaneously hypertensive rats.
Yu X, Yang Z, Ma Z … +2 more , Yan R, Zhang J
Microvasc Res · 2025 Sep · PMID 40664331 · Publisher ↗
This study aimed to explore the effects of Angiotensin 1-7 (Ang1-7) on electrophysiological remodeling of hypertensive hypertrophic myocardium in spontaneously hypertensive rats (SHR). Thirty male SHR rats were equally d...
This study aimed to explore the effects of Angiotensin 1-7 (Ang1-7) on electrophysiological remodeling of hypertensive hypertrophic myocardium in spontaneously hypertensive rats (SHR). Thirty male SHR rats were equally divided into three groups: SHR control group (SHRC) treated with saline; Ang1-7 group (SHR-A) treated with Ang1-7[25 μg·(kg min)] and Ang1-7 blocker group (SHRB) treated with A779 [72 μg·(kg min)]. Wistar-Kyoto (WKY) rats (n = 10) were used as a normotensive group. The treatment period was 5 weeks. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. Echocardiography was used to evaluate cardiac function. The ventricular myocytes were isolated for evaluation of electrophysiological remodeling of myocardium using microelectrode and patch clamp techniques. When compared with those in WKY rats before treatment, systolic and diastolic pressures were significantly higher in SHR (P < 0.01 and P < 0.001 respectively), left ventricular end-diastolic diameter (LVEDd) was significantly lower (P < 0.05), while diastolic interventricular septum thickness (IVSd), diastolic left ventricular posterior wall thickness (LVPWd) were significantly greater in SHR (P < 0.01). After 5 weeks of treatment, compared with SHR-C group, SBP, DBP, IVSd, LVPWd in SHR-A group were lower significantly (P < 0.05), while SBP in SHR-B group was significantly higher (P < 0.05). Compared with WKY group, the resting potential (RP), action potential amplitude (APA) and transient sodium current (I) in SHR group were significantly lower (P < 0.05), and the action potential duration (APD, APD and APD) in SHR group was greater (P < 0.05). After Ang1-7 intervention, RP, APA and I were significantly greater in SHR-A than those in SHR-C (P < 0.05), and APD in SHR-A significantly lower than that in SHR-C (P < 0.05). Taken together, these results demonstrated that Ang1-7 can not only decrease the blood pressure, but reverse the myocardial hypertrophy and electrophysiological remodeling as well in SHR rats.
Acute effects of belt electrode-skeletal muscle electrical stimulation on microvascular responsiveness of the gastrocnemius muscle in healthy young men.
Tamiya H, Kawashiri H, Miyamoto T … +3 more , Kurosawa Y, Hamaoka T, Tsubaki A
Microvasc Res · 2025 Sep · PMID 40639754 · Publisher ↗
PURPOSE: Belt electrode-skeletal muscle electrical stimulation (B-SES) improves muscle strength, mass, and exercise tolerance. However, its effects on skeletal muscle microvascular responsiveness remain unclear. In this...
PURPOSE: Belt electrode-skeletal muscle electrical stimulation (B-SES) improves muscle strength, mass, and exercise tolerance. However, its effects on skeletal muscle microvascular responsiveness remain unclear. In this study, we investigated the acute effects of a single B-SES session on gastrocnemius microvascular responsiveness in healthy young men. METHODS: In this randomized crossover study, 12 healthy young men (mean age: 20.8 ± 1.0 years) underwent two 20-min conditions: electrical stimulation at the sensory threshold (Sham, n = 12) and at the maximum intensity not causing discomfort (B-SES, n = 12). Gastrocnemius metabolic rate (tissue oxygen saturation [StO] downslope) and microvascular reperfusion rate (StO upslope) were assessed using near-infrared spectroscopy and a vascular occlusion test. RESULTS: In the B-SES condition, the StO downslope significantly steepened (Pre: -0.15 ± 0.03 %·s, Post: -0.20 ± 0.03 %·s, p = 0.002). The StO upslope also significantly steepened (Pre: 1.58 ± 0.52 %·s, Post: 2.56 ± 0.71 %·s, p < 0.001). A significant negative correlation was observed between the StO downslope and StO upslope (r = -0.581, p = 0.047). No significant changes were observed in the Sham condition. CONCLUSIONS: A single B-SES session applied to the lower extremity significantly increased gastrocnemius metabolic rate and was associated with enhanced microvascular reperfusion. These findings suggest B-SES may be a useful therapeutic approach to improving microvascular responsiveness, particularly in individuals with limited exercise capacity.
Letter to the editor: "Pitfalls in the assessment of microcirculation".
Dubin A
Microvasc Res · 2025 Sep · PMID 40633806 · Publisher ↗
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Kinetics of thromboxane A2 receptor-driven vascular tone in the cerebral cortex ex vivo.
Woodruff S, Zimmerman B, Elk KJ … +3 more , Jenks JE, Bojovic D, Mishra A
Microvasc Res · 2025 Sep · PMID 40614800 · Full text
Ex vivo imaging in acute cortical brain slices is a valuable tool to assess neurovascular coupling and is particularly useful for studying active, local changes in microvascular compartments in isolation from upstream or...
Ex vivo imaging in acute cortical brain slices is a valuable tool to assess neurovascular coupling and is particularly useful for studying active, local changes in microvascular compartments in isolation from upstream or downstream changes in flow. However, the lack of vascular perfusion pressure ex vivo results in loss of vascular tone, which must be restored prior to experiments to unmask dilatory signals. The thromboxane A2 receptor agonist U46619 is a widely used preconstrictor, yet its dose-response properties and kinetics of action on different vascular segments are not fully known. Here, we characterize the effects of U46619 on cortical arterioles and capillaries in ex vivo slices from rats and mice. Dose response curves tested in acute rat brain slices using 0 to 1000 nM U46619 showed that maximal constriction is reached at ∼300 nM in both arterioles and capillaries. Extended application of 200 nM U46619 (∼66 % maximal dose) over 2 h revealed that, on average, capillaries constrict faster than arterioles in rat brain slices. Cross-species examination in mouse tissue showed that vessels in mouse brain slices respond faster and constrict stronger on average than in rat brain slices, and that mouse capillaries also constrict faster than mouse arterioles. Our observations suggest that near-maximal preconstriction can be achieved in ex vivo experiments using 200-300 nM U46619, with a minimum incubation time of 20 min for studies involving capillaries and at least 30 min for studies involving arterioles.
Influence of isometric RPE-clamp exercise on fatigability, muscle oxygenation dynamics, and microvascular function in healthy young adults.
Kwak M, Benitez B, Mitchinson CJ … +2 more , Snell ER, Bergstrom HC
Microvasc Res · 2025 Sep · PMID 40614799 · Publisher ↗
PURPOSE: This study investigated fatigability, reflected by torque responses and time to task failure (TTF), and time course of muscle oxygenation (SmO) dynamics, as well as microvascular function assessed by near-infrar...
PURPOSE: This study investigated fatigability, reflected by torque responses and time to task failure (TTF), and time course of muscle oxygenation (SmO) dynamics, as well as microvascular function assessed by near-infrared spectroscopy-vascular occlusion test (NIRS-VOT), in response to low-intensity, isometric forearm flexion anchored to a constant rating of perceived exertion (RPE) level of 3 (0-10 scale). METHODS: Twenty-five healthy young adults (22.9 ± 4.8 yr) completed a pre-exercise VOT, maximal voluntary isometric contraction (MVIC), and RPE-clamp exercise (RPE = 3), followed by post-exercise MVIC and VOT. Initial torque, TTF, and SmO dynamics were recorded during the RPE-clamp exercise. The time course of SmO was analyzed in 5 % TTF segments. During the VOTs, slope 1 (desaturation rate), minimum SmO, slope 2 (reperfusion rate), maximum SmO, and area under the curve (AUC) were recorded. RESULTS: MVIC torque significantly decreased from pre- to post-exercise (-13.9 % ± 14.0 %; p < 0.001). Initial torque was 23.3 ± 10.3 % MVIC, and TTF was 436.3 ± 252.0 s. SmO declined significantly from 0 % to 5 % TTF (p = 0.005), but returned to the initial value and remained stable across subsequent time intervals. Compared to pre-VOT, post-VOT exhibited significantly lower slope 1 (p < 0.001) and minimum SmO (p = 0.002), and greater maximum SmO (p = 0.013), while slope 2 (p = 0.065) and AUC (p = 0.379) were unchanged. CONCLUSIONS: During the RPE-clamp exercise, the voluntary reduction in torque to maintain the assigned RPE likely resulted in stable muscle oxygen availability, preventing the development of hypoxic stimulus needed to enhance microvascular responsiveness. However, the low-intensity isometric RPE-clamp exercise combined with a post-VOT may enhance muscle aerobic metabolism through sustained oxygen utilization.
Structural and causal links between retinal vascular geometry and neural layer thickness.
Yusufu M, Weinreb RN, Kang M … +5 more , Vingrys AJ, Shang X, Zhang L, Shi D, He M
Microvasc Res · 2025 Sep · PMID 40582562 · Publisher ↗
PURPOSE: To investigate structural relationships between retinal vasculometry from color fundus photography (CFP) and neural layers obtained from Optical Coherence Tomography (OCT) scans. METHODS: This cross-sectional st...
PURPOSE: To investigate structural relationships between retinal vasculometry from color fundus photography (CFP) and neural layers obtained from Optical Coherence Tomography (OCT) scans. METHODS: This cross-sectional study used the Retina-based Microvascular Health Assessment System (RMHAS) to extract retinal vascular measurements in the 6*6 mm area centered on the macular region and analyzed their associations with OCT parameters. We investigated both pairwise correlations between individual retinal layers and vascular parameters and associations between sets of variables. Mendelian randomization was employed to investigate potential causality. RESULTS: Data from 67,918 eyes of 43,029 participants were included. Among neural layers, Ganglion Cell-Inner Plexiform Layer (GC-IPL) showed the most notable correlations with vascular Density and Complexity (r = 0.199 for arterial Vessel Area Density and r = 0.175 for Number of Segments). Inner Nuclear Layer (INL) thickness correlated with Width (r = 0.122) and arterial Vessel Area Density (r = 0.127). Mendelian randomization indicated a bidirectional causal relationship. Genetically predicted higher Vessel Density was associated with increased thickness across various retinal layers, with standardized effect size of 1.50 on Inner Segment/Outer Segment + Photoreceptor Segment thickness. Genetically predicted increases in retinal layer thicknesses, particularly the Outer Plexiform Layer, were linked to higher Vessel Density (standardized effect size 0.45) and Fractal Dimension (standardized effect size 0.48). CONCLUSIONS: GC-IPL and INL were positively associated with vascular Density and Caliber. Multidimensional relationships indicate a complementary nature between retinal vascular and neural parameters, highlighting their value as a composite biomarker. Mendelian Randomization uncovered a bidirectional causal relationship, providing insights into novel therapeutic approaches targeting vascular and neuronal components.
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