Vascular Pharmacology[JOURNAL]
Sun
200 papers
Prevalence of antiphospholipid antibodies in COVID-19 patients: A meta-analysis.
Jin E, Li B, Wang X … +3 more , Yan R, Yan C, Gao Y
Vascul Pharmacol · 2025 Mar · PMID 39638272 · Publisher ↗
OBJECTIVE: In some reports, antiphospholipid antibodies (aPL) prevalence is higher in COVID-19 patients. This study intended to compare aPL prevalence between COVID-19 patients and healthy controls, and differences in aP...
OBJECTIVE: In some reports, antiphospholipid antibodies (aPL) prevalence is higher in COVID-19 patients. This study intended to compare aPL prevalence between COVID-19 patients and healthy controls, and differences in aPL types using meta-analysis. METHODS: This work retrieved published literature about association between COVID-19 and aPL from Embase, Web of Science, PubMed, and The Cochrane Library databases. The observation group was COVID-19 patients, and the control group was healthy individuals. Outcome measures contained any of following aPLs: classic aPL: anti-cardiolipin antibodies (aCL) and anti-β2-glycoprotein-1 antibodies (Anti-β2GP1); other non-criteria aPL: anti-phosphatidylserine/prothrombin antibodies (aPS/PT) and anti-annexin-V antibodies (AnV). Meta-analysis was done on Review Manager 5.4. RESULTS: 10 studies involving 2288 patients were deemed eligible for inclusion. The results of the meta-analysis showed that the prevalence of Classic aPL and Any aPL in the COVID-19 group was significantly higher than in the healthy group (Classic aPL, RR = 2.55, 95 % CI = 1.83-3.55, P < 0.00001; Any aPL, RR = 2.34, 95 % CI = 1.46-3.77, P = 0.0005). Anti-β2GP1 IgA antibodies were the most common aPL in COVID-19 patients, with a significantly higher prevalence than in the healthy group (RR = 4.26, 95 % CI = 2.84-6.40, P < 0.00001). The prevalence of the four types of IgM aPL was significantly higher in the COVID-19 group compared to the healthy group, while there was no significant difference in aPL IgG between the two groups. CONCLUSION: The prevalence of aPL in COVID-19 patients was significantly higher than in the healthy control group. IgM aPL was more easily detectable in the early stages of COVID-19 infection, while IgG aPL may be of more concern in the later time points of the immune epidemiology following SARS-CoV-2 infection.
New insights into the pharmacological inhibition of SRF activity: Key inhibitory targets and mechanisms.
Wong D, Qiu H
Vascul Pharmacol · 2024 Dec · PMID 39586415 · Full text
Serum Response Factor (SRF) is a critical regulatory transcription factor widely expressed across cell types and is essential for animal survival. Excessive SRF activity has been linked to various pathological conditions...
Serum Response Factor (SRF) is a critical regulatory transcription factor widely expressed across cell types and is essential for animal survival. Excessive SRF activity has been linked to various pathological conditions and diseases, including cardiovascular diseases, cancers and neurodegenerative disorders, making the inhibition of SRF hyperactivity a promising therapeutic strategy. This review summarizes recent advancements in the discovery and development of SRF inhibitors, their regulatory mechanisms, and their respective molecular foundations. These insights deepen our understanding of current therapeutic potentials, paving the way for novel approaches to treat diseases associated with SRF hyperactivity.
Patterns of medication use and potential drug-drug interactions in post-PCI patients: A study from Iran.
Vafa RG, Vardanjani HM, Kojuri J
Vascul Pharmacol · 2024 Dec · PMID 39581248 · Publisher ↗
BACKGROUND: Post-percutaneous coronary intervention (PCI) patients often require complex medication regimens to prevent adverse cardiovascular events. However, these regimens can lead to potential drug-drug interactions...
BACKGROUND: Post-percutaneous coronary intervention (PCI) patients often require complex medication regimens to prevent adverse cardiovascular events. However, these regimens can lead to potential drug-drug interactions (pDDIs) and polypharmacy, posing significant clinical challenges. This study aims to evaluate the pattern of medication use, prevalence, and correlates of pDDIs and polypharmacy among post-PCI patients in Shiraz, Iran. METHODS: A cross-sectional study was conducted on 9019 PCI patients in Shiraz. Patient data, including demographics, medical history, and medication lists, were collected and analyzed. The Anatomical Therapeutic Chemical (ATC) classification system was applied. pDDIs were identified using the Lexicomp database, and their severity was classified. Factors associated with significant pDDIs and polypharmacy were assessed using multivariable modeling. RESULTS: The study found that 91.6 % of patients received statin prescriptions and 94.5 % were on antiplatelet therapy. Notably, 82.8 % were identified with at least one pDDI, with 80.4 % having significant interactions (Categories C, D, or X). Common potential interactions included aspirin with clopidogrel and rosuvastatin. Polypharmacy was prevalent in 73.6 % of patients, associated with higher risks of interactions. Factors such as polypharmacy, male gender, diabetes mellitus, and heart failure were significant predictors of pDDIs. CONCLUSIONS: The study underscores the high prevalence of pDDIs and polypharmacy among post-PCI patients, revealing a critical gap between clinical guidelines and drug interaction databases. Updating interaction databases to reflect current clinical practices and enhancing collaboration between database developers and guideline authors are essential for improving medication safety and patient outcomes.
Sotatercept: New drug on the horizon of pulmonary hypertension.
Madonna R, Biondi F
Vascul Pharmacol · 2024 Dec · PMID 39571875 · Publisher ↗
Sotatercept (brand name WINREVAIR, developed by Merck) is an activin receptor type IIA-Fc (ActRIIA-Fc), working by sequestering free activins. Sotatercept restores the balance between the activin proliferative pathway an...
Sotatercept (brand name WINREVAIR, developed by Merck) is an activin receptor type IIA-Fc (ActRIIA-Fc), working by sequestering free activins. Sotatercept restores the balance between the activin proliferative pathway and the bone morphogenic protein (BMP) antiproliferative pathway in the pulmonary arterial cirulation. Sotatercept recently received approval in the USA and in Europe for the treatment of adults with pulmonary arterial hypertension (PAH) Group 1, on top of background PAH therapy to increase exercise capacity, improve WHO functional class and reduce the risk of clinical worsening events. Nevertheless, several studies are ongoing to investigate the potential adverse reactions of the drug especially at the haematological level. We provide an overview of the clinical and preclinical evidence of the targeting the activing pathway through sotatercept on the treatment of PAH. We also discuss what other possibilities there are for the application of sotatercept in the setting of pulmonary hypertension other than PAH Group 1.
LncRNA MYOSLID contributes to PH via targeting BMPR2 signaling in pulmonary artery smooth muscle cell.
Chen Y, Li Y, Leng B … +4 more , Cao C, Wu G, Ye S, Deng L
Vascul Pharmacol · 2024 Dec · PMID 39549862 · Publisher ↗
BACKGROUND/OBJECTIVE: The pathogenesis and vascular remodeling during pulmonary hypertension (PH) have been associated with dysregulation of bone morphogenetic protein receptor type 2 (BMPR2) and transforming growth fact...
BACKGROUND/OBJECTIVE: The pathogenesis and vascular remodeling during pulmonary hypertension (PH) have been associated with dysregulation of bone morphogenetic protein receptor type 2 (BMPR2) and transforming growth factor-β (TGF-β) signaling in pulmonary artery smooth muscle cells (PASMCs). Evidence suggests that the human-specific lncRNA MYOSLID is a transcriptional target of the TGF-β/SMAD pathway. In this study, we investigated the involvement of MYOSLID in the pathogenesis of PH. METHODS: Lung tissues from PH patients and rat PH models were analyzed to assess clinical relevance. RNA-Seq was performed to identify target genes. Pulmonary artery smooth muscle cells (PASMCs) were used to evaluate function and underlying mechanisms. RESULTS: RNA-Seq analysis of PASMCs stimulated by TGF-β1 revealed significantly dysregulated lncRNAs. MYOSLID expression was markedly elevated in lung tissues from PH patients and in PASMCs stimulated with TGF-β1. Mechanistically, loss of MYOSLID inhibited the TGF-β pathway by reducing SMAD2/3 PHosphorylation and activated the BMPR2 pathway by enhancing SMAD1/5/9 phosphorylation and increasing ID genes expression in PASMCs. DAZAP2, a target gene of MYOSLID, functions as an inhibitor of BMPR2 signaling. Moreover, DAZAP2 expression was significantly elevated in lung tissues from PH patients and rat PH models. Functionally, knockdown of MYOSLID and DAZAP2 reduced proliferation, migration, and apoptosis resistance in PASMCs. CONCLUSION: The activation of the MYOSLID-DAZAP2-BMPR2 axis contributes to pulmonary vascular remodeling, and targeting MYOSLID and DAZAP2 may represent novel therapeutic strategies for PH treatment.
Prolonged L-NAME exposure changes the vasodilator factor from NO to HO in human arterioles in response to A23187.
Zinkevich NS, Drachuk K, Zhang DX
Vascul Pharmacol · 2024 Dec · PMID 39537001 · Full text
The Ca ionophore A23187 induces endothelium-dependent and non-receptor-mediated vasodilation in human adipose arterioles (HAAs). The purpose of this study was to determine the mechanism of A23187-induced dilation in HAAs...
The Ca ionophore A23187 induces endothelium-dependent and non-receptor-mediated vasodilation in human adipose arterioles (HAAs). The purpose of this study was to determine the mechanism of A23187-induced dilation in HAAs from patients with and without coronary artery disease (CAD). HAAs were freshly isolated from adipose tissues obtained from non-CAD (n = 25) and CAD (n = 14) patients, and vascular reactivity was studied by videomicroscopy. No difference in baseline dose response to A23187 was observed between non-CAD and CAD subjects. However, acute (30 min) incubation with N(omega)-nitro-l-arginine methyl ester (L-NAME), NO synthase inhibitor strongly reduced A23187-induced dilation in non-CAD arterioles, while catalase, an HO scavenger, largely abolished dilation in CAD. Surprising, prolonged (90 min) incubation with L-NAME restored A23187 response in non-CAD subjects, which was subsequently inhibited by catalase. The action of prolonged L-NAME exposure was not reversible after washing with Krebs while the effect of acute L-NAME exposure was largely reversible. To further determine the role of mitochondria-derived ROS in A23187-induced dilation, arterioles were treated with rotenone, an inhibitor of complex I of the electron transport chain. Rotenone abolished A23187 response in CAD patients and in non-CAD arterioles after prolonged L-NAME, but not in non-CAD controls. These data indicate that NO contributes to A23187-induced dilation in HAAs from non-CAD patients and HO contributes to the dilation in CAD patients. Prolonged L-NAME exposure induces a NO-HO switch in the mechanism of dilation in non-CAD subjects. Moreover, the effect of prolonged L-NAME exposure is not readily reversible, while the action of acute L-NAME exposure is reversible.
Functional characterization of human IL-8 in vascular stenosis using a novel humanized transgenic mouse model.
Zhang W, Pan L, Wu X … +3 more , Slivano OJ, Dong K, Long X
Vascul Pharmacol · 2024 Dec · PMID 39486776 · Full text
IL-8 (aka interleukin 8, CXCL8) is a prototypic cytokine that is highly expressed in the diseased vessel wall and its plasma concentration is strongly associated with cardiovascular events. However, whether IL-8 plays a...
IL-8 (aka interleukin 8, CXCL8) is a prototypic cytokine that is highly expressed in the diseased vessel wall and its plasma concentration is strongly associated with cardiovascular events. However, whether IL-8 plays a causative role in cardiovascular diseases remains largely unknown. In this study we used a human IL-8 transgenic (Tg) mouse strain with a bacterial artificial chromosome (BAC) integrated into its genome. This BAC encompasses 166 kb of sequence encompassing the human IL-8 gene locus as well as upstream and downstream DNA sequences containing regulatory elements. This BAC ensured a pathophysiologically regulated, rather than forced constitutive, expression of human IL-8 in the mouse. Tg mice were subjected to complete carotid ligation injury. IL-8 was highly expressed in the ligation-injured carotid artery from 3 days until 2 weeks after injury. As a result, exacerbated neointimal hyperplasia and increased Mac2 and PCNA positive cells were observed in Tg mice. To further confirm its role in promoting neointimal formation, IL-8 was neutralized by anti-IL8 treatment at the ligation site. Consequently, the size of neointima was significantly reduced. Our results provided new insights into the regulation and function of IL-8 in response to vascular insult and during neointima formation.
Lack of AMP-activated protein kinase-α1 reduces nitric oxide synthesis in thoracic aorta perivascular adipose tissue.
Hwej A, Al-Ferjani A, Alshuweishi Y … +3 more , Naji A, Kennedy S, Salt IP
Vascul Pharmacol · 2024 Dec · PMID 39433170 · Publisher ↗
OBJECTIVE: Perivascular adipose tissue (PVAT) releases anti-contractile bioactive molecules including NO. PVAT anti-contractile activity is attenuated in mice lacking AMPKα1 (AMP-activated protein kinase-α1). As AMPK reg...
OBJECTIVE: Perivascular adipose tissue (PVAT) releases anti-contractile bioactive molecules including NO. PVAT anti-contractile activity is attenuated in mice lacking AMPKα1 (AMP-activated protein kinase-α1). As AMPK regulates endothelial NO synthase (eNOS) activity in cultured cells, NO synthesis was examined in PVAT from AMPKα1 knockout (KO) mice. METHODS AND RESULTS: Endothelium-denuded thoracic or abdominal aortic rings were isolated from wild type (WT) and KO mice. NOS inhibition enhanced vasoconstriction in PVAT-intact thoracic aortic rings from mice of either genotype yet had no effect on abdominal rings as assessed by wire myography. Thoracic aorta PVAT exhibited increased NO production, NOS activity and levels of the brown adipose tissue marker uncoupling protein-1 (UCP1) compared to abdominal PVAT. In KO mice, NO production was significantly reduced in thoracic but not abdominal PVAT. Reduced NO production in KO thoracic PVAT was not due to altered levels or phosphorylation of eNOS but was associated with increased caveolin-1:eNOS association and caveolin-1 Tyr14 phosphorylation. A peptide that disrupts eNOS:caveolin-1 association increased NO synthesis and reduced vasoconstriction of PVAT-intact thoracic but not abdominal aortic rings. KO thoracic PVAT also exhibited reduced UCP1 levels. CONCLUSIONS: Murine thoracic aorta PVAT exhibits higher NO synthesis and UCP1 levels than abdominal aortic PVAT. Downregulation of AMPK suppresses NO synthesis which may contribute to the reduced anticontractile activity and reduced brown adipose tissue phenotype of KO thoracic PVAT. The mechanism underlying the effect of AMPK downregulation likely results from increased caveolin-1:eNOS association associated with caveolin-1 Tyr14 phosphorylation.
Different gene expression patterns between mouse and human brain pericytes revealed by single-cell/nucleus RNA sequencing.
Miao Y, Li W, Jeansson M … +3 more , Mäe MA, Muhl L, He L
Vascul Pharmacol · 2024 Dec · PMID 39423955 · Publisher ↗
AIMS: Pericytes in the brain play important roles for microvascular physiology and pathology and are affected in neurological disorders and neurodegenerative diseases. Mouse models are often utilized for pathophysiology...
AIMS: Pericytes in the brain play important roles for microvascular physiology and pathology and are affected in neurological disorders and neurodegenerative diseases. Mouse models are often utilized for pathophysiology studies of the role of pericytes in disease; however, the translatability is unclear as brain pericytes from mouse and human have not been systematically compared. In this study, we investigate the similarities and differences of brain pericyte gene expression between mouse and human. Our analysis provides a comprehensive resource for translational studies of brain pericytes. METHODS: We integrated and compared four mouse and human adult brain pericyte single-cell/nucleus RNA-sequencing datasets derived using two single-cell RNA sequencing platforms: Smart-seq and 10x. Gene expression abundance and specificity were analyzed. Pericyte-specific/enriched genes were assigned by comparison with endothelial cells present in the same datasets, and mouse and human pericyte transcriptomes were subsequently compared to identify species-specific genes. RESULTS: An overall concordance between pericyte transcriptomes was found in both Smart-seq and 10x data. 206 orthologous genes were consistently differentially expressed between human and mouse from both platforms, 91 genes were specific/up-regulated in human and 115 in mouse. Gene ontology analysis revealed differences in transporter categories in mouse and human brain pericytes. Importantly, several genes implicated in human disease were expressed in human but not in mouse brain pericytes, including SLC6A1, CACNA2D3, and SLC20A2. CONCLUSIONS: This study provides a systematic illustration of the similarities and differences between mouse and human adult brain pericytes.
Examining the controversies in venous thromboembolism prophylaxis for vascular surgery patients: A critical review.
Fang T, Zhang R, Li Y
Vascul Pharmacol · 2024 Dec · PMID 39419294 · Publisher ↗
BACKGROUND: Venous thromboembolism (VTE) is a significant concern in vascular surgery due to its potentially severe consequences. Effective prophylactic measures are essential to minimize the risks associated with VTE. H...
BACKGROUND: Venous thromboembolism (VTE) is a significant concern in vascular surgery due to its potentially severe consequences. Effective prophylactic measures are essential to minimize the risks associated with VTE. However, considerable controversy remains regarding the optimal strategies for VTE prevention in patients undergoing vascular procedures. METHODS: This review critically analyzes key clinical research, guidelines, and expert opinions to explore the advantages and limitations of various VTE prophylaxis approaches. The pharmacological and mechanical methods are explored, with a focus on balancing the risk of VTE against the potential for bleeding complications, particularly in high-risk patients. RESULTS: The review addresses controversial issues such as the choice of anticoagulants, dosage, timing, and duration of prophylaxis. The lack of consensus in existing guidelines and the variability in clinical practice regarding VTE prevention in vascular surgery patients is highlighted. The role of patient-specific risk factors, including the use of intraoperative anticoagulation and bleeding risks, is also examined. CONCLUSION: This review provides a comprehensive evaluation of VTE prophylaxis strategies in vascular surgery, emphasizing the need for individualized, evidence-based approaches. Clarifying these controversies is crucial for optimizing patient outcomes and minimizing both thrombotic and hemorrhagic complications.
Bioactive lipids improve serum HDL and PON1 activities in coronary artery disease patients: Ex-vivo study.
Khattib A, Shmet M, Levi A … +3 more , Hayek T, Halabi M, Khatib S
Vascul Pharmacol · 2024 Dec · PMID 39419293 · Publisher ↗
BACKGROUND: Atherosclerotic cardiovascular disease (CVD) remains a leading cause of vascular disease worldwide. Atherosclerosis is characterized by the accumulation of lipids and oxidized lipids on the blood vessel walls...
BACKGROUND: Atherosclerotic cardiovascular disease (CVD) remains a leading cause of vascular disease worldwide. Atherosclerosis is characterized by the accumulation of lipids and oxidized lipids on the blood vessel walls. Coronary artery disease (CAD) is the most common display of atherosclerotic CVD. OBJECTIVES: We investigated the effects of the bioactive lipids as lyso-diacylglyceryltrimethylhomoserine (lyso-DGTS (20,5,0)) and its derivative oleoyl-N-trimethyl homoserine amide (oleoyl amide-MHS) on the properties and functionality of HDL and paraoxonase 1 (PON1) activities in the serum of individuals who exhibited arterial plaque as observed by coronary CT angiography (CCTA). METHODS: The study included two independent groups comprising 40 patients who had undergone arterial CCTA scans at Ziv Medical Center for various medical indications. The CAD group included 20 patients with coronary artery plaques with luminal stenosis of more than 50 % in a major coronary vessel. The control group consisted of 20 healthy patients (patients without artery plaques). RESULTS: Serum samples from CAD patients exhibited lower serum PON1 and cholesterol efflux activities and higher pro-inflammatory than the control group. HDL isolated from CAD patients contains elevated levels of oxidizing lipids (specifically lyso- phosphatidyl ethanolamines and lyso-phosphocholines(compared to the control. However, incubation of the CAD patients' serum with lyso-DGTS and oleoyl amide-MHS restored the antiatherogenic activities of HDL. The lipids increased serum PON1 activities, enhanced apoB-depleted serum cholesterol-efflux activity, and elevated the serum's anti-inflammatory properties. CONCLUSIONS: The results of the present study suggest the potential of the bioactive lipids lyso-DGTS and oleoyl amide-MHS to attenuate atherosclerosis via the improvement of dysfunctional HDL properties and PON1 activities. Further, in-vivo experiments are needed to assess the athero-protective effect of the lipids.
Altered copper transport in oxidative stress-dependent brain endothelial barrier dysfunction associated with Alzheimer's disease.
Hossain MS, Das A, Rafiq AM … +8 more , Deák F, Bagi Z, Outlaw R, Sudhahar V, Yamamoto M, Kaplan JH, Ushio-Fukai M, Fukai T
Vascul Pharmacol · 2024 Dec · PMID 39317307 · Full text
Oxidative stress and blood-brain barrier (BBB) disruption due to brain endothelial barrier dysfunction contribute to Alzheimer's Disease (AD), which is characterized by beta-amyloid (Aβ) accumulation in senile plaques. C...
Oxidative stress and blood-brain barrier (BBB) disruption due to brain endothelial barrier dysfunction contribute to Alzheimer's Disease (AD), which is characterized by beta-amyloid (Aβ) accumulation in senile plaques. Copper (Cu) is implicated in AD pathology and its levels are tightly controlled by several Cu transport proteins. However, their expression and role in AD, particularly in relation to brain endothelial barrier function remains unclear. In this study, we examined the expression of Cu transport proteins in the brains of AD mouse models as well as their involvement in Aβ42-induced brain endothelial barrier dysfunction. We found that the Cu uptake transporter CTR1 was upregulated, while the Cu exporter ATP7A was downregulated in the hippocampus of AD mouse models and in Aβ42-treated human brain microvascular endothelial cells (hBMECs). In the 5xFAD AD mouse model, Cu levels (assessed by ICP-MS) were elevated in the hippocampus. Moreover, in cultured hBMECs, Aβ42-induced reactive oxygen species (ROS) production, ROS-dependent loss in barrier function (measured by transendothelial electrical resistance), and tyrosine phosphorylation of CDH5 were all inhibited by either a membrane permeable Cu chelator or by knocking down CTR1 expression. These findings suggest that dysregulated expression of Cu transport proteins may lead to intracellular Cu accumulation in the AD brain, and that Aβ42 promotes ROS-dependent brain endothelial barrier dysfunction and CDH5 phosphorylation in a CTR1-Cu-dependent manner. Our study uncovers the critical role of Cu transport proteins in oxidative stress-related loss of BBB integrity in AD.
Gaps in evidence in the treatment of prevalent patients with pulmonary arterial hypertension at intermediate risk: An expert consensus.
Manzi G, Benza RL, Argiento P … +21 more , Casu G, Corda M, Correale M, D'Alto M, Galgano G, Garascia A, Ghio S, Gomberg-Maitland M, Mulé M, Paciocco G, Papa S, Prati D, Preston IR, Raineri C, Romeo E, Scelsi L, Stolfo D, Vitulo P, White RJ, Badagliacca R, Vizza CD
Vascul Pharmacol · 2024 Dec · PMID 39265796 · Publisher ↗
Despite the innovations introduced in the 2022 European Society of Cardiology/European Respiratory Society Guidelines on Pulmonary Hypertension, risk discrimination and management of pulmonary arterial hypertension (PAH)...
Despite the innovations introduced in the 2022 European Society of Cardiology/European Respiratory Society Guidelines on Pulmonary Hypertension, risk discrimination and management of pulmonary arterial hypertension (PAH) patients at intermediate risk still represents a grey zone. Additionally, clinical evidence derived from currently available studies is limited. This expert panel survey intends to aid physicians in choosing the best therapeutic strategy for patients at intermediate risk despite ongoing oral therapy. An expert panel of 24 physicians, specialized in cardiology and/or pulmonology with expertise in handling all drugs available for the treatment of PAH participated in the survey. All potential therapeutic options for patients at intermediate risk were explored and analyzed to produce graded consensus statements regarding: the switch from endothelin receptor antagonist (ERA) or phosphodiesterase 5 inhibitor (PDE5i) to another oral drug of the same class; the addition of a drug targeting the prostacyclin pathway administered by different routes; the switch from PDE5i to riociguat.
Recent advances in serum response factor posttranslational modifications and their therapeutic potential in cardiovascular and neurological diseases.
Visconti A, Qiu H
Vascul Pharmacol · 2024 Sep · PMID 39209126 · Full text
Serum Response Factor (SRF) is a key regulatory transcription factor present in various cell types throughout the body, playing essential roles in cellular functions under physiological conditions. Mutations and abnormal...
Serum Response Factor (SRF) is a key regulatory transcription factor present in various cell types throughout the body, playing essential roles in cellular functions under physiological conditions. Mutations and abnormal expression of SRF have been linked to the development of various diseases and disorders. Recent evidence highlights that post-translational modifications (PTMs) are critical for regulating SRF function in different cell types and contribute to disease pathogenesis. Targeting SRF-related PTMs is emerging as a promising therapeutic approach for treating SRF-associated diseases. In this review, we summarize recent advances in understanding SRF PTMs and their underlying regulatory mechanisms. We also explore the implications of SRF-PTM in related cardiovascular and neurological diseases and their potential for therapeutic intervention. This information underscores the significance of SRF PTMs in both physiological and pathological contexts, enhancing our understanding of disease mechanisms and paving the way for the development of novel therapeutic strategies.
Matrix metalloproteinases in aortic dissection.
Zhou S, Ma B, Luo M
Vascul Pharmacol · 2024 Sep · PMID 39182633 · Publisher ↗
Aortic dissection, characterized by a high immediate mortality, is primarily caused by excessive bleeding within the walls of the aorta or a severe tear within the intimal layer of the aorta. Inflammation, as well as oxi...
Aortic dissection, characterized by a high immediate mortality, is primarily caused by excessive bleeding within the walls of the aorta or a severe tear within the intimal layer of the aorta. Inflammation, as well as oxidative stress and the degradation of extracellular matrix (ECM), are significant factors in the development and occurrence of aortic dissection. Matrix metalloproteinases (MMPs) are pivotal enzymes responsible for degrading the ECM. Inflammatory factors and oxidants can interact with MMPs, indicating the potential significance of MMPs in aortic dissection. A substantial body of evidence indicates that numerous MMPs are significantly upregulated in aortic dissection, playing a critical role in ECM degradation and the pathogenesis of aortic dissection. Furthermore, targeting these enzymes has demonstrated potential in facilitating ECM restoration and reducing the incidence of aortic dissection. This review initially provides a brief overview of MMP biology before delving into their expression patterns, regulatory mechanisms, and therapeutic applications in aortic dissection. A profound comprehension of the catabolic pathways associated with aortic dissection is imperative for the future development of potential preventive or therapeutic bio-interventions for aortic dissection.
Macrophages in vascular disease: Roles of mitochondria and metabolic mechanisms.
Mackay CDA, Meechem MB, Patel VB
Vascul Pharmacol · 2024 Sep · PMID 39181483 · Publisher ↗
Macrophages are a dynamic cell type of the immune system implicated in the pathophysiology of vascular diseases and are a major contributor to pathological inflammation. Excessive macrophage accumulation, activation, and...
Macrophages are a dynamic cell type of the immune system implicated in the pathophysiology of vascular diseases and are a major contributor to pathological inflammation. Excessive macrophage accumulation, activation, and polarization is observed in aortic aneurysm (AA), atherosclerosis, and pulmonary arterial hypertension. In general, macrophages become activated and polarized to a pro-inflammatory phenotype, which dramatically changes cell behavior to become pro-inflammatory and infiltrative. These cell types become cumbersome and fail to be cleared by normal mechanisms such as autophagy. The result is a hyper-inflammatory environment causing the recruitment of adjacent cells and circulating immune cells to further augment the inflammatory response. In AA, this leads to excessive ECM degradation and chemokine secretion, ultimately causing macrophages to dominate the immune cell landscape in the aortic wall. In atherosclerosis, monocytes are recruited to the vascular wall, where they polarize to the pro-inflammatory phenotype and induce inflammatory pathway activation. This leads to the development of foam cells, which significantly contribute to neointima and necrotic core formation in atherosclerotic plaques. Pro-inflammatory macrophages, which affect other vascular diseases, present with fragmented mitochondria and corresponding metabolic dysfunction. Targeting macrophage mitochondrial dynamics has proved to be an exciting potential therapeutic approach to combat vascular disease. This review will summarize mitochondrial and metabolic mechanisms of macrophage activation, polarization, and accumulation in vascular diseases.
Characterization of a novel mitophagy-related 5-genes signature for diagnosis of acute myocardial infarction.
Xu Y, Zhu W, Su Y … +8 more , Ma T, Zhang Y, Pan X, Huang R, Li Y, Zuo K, Ong SB, Xu D
Vascul Pharmacol · 2024 Sep · PMID 39159737 · Publisher ↗
Myocardial infarction (MI) and the ensuing heart failure (HF) remain the main cause of morbidity and mortality worldwide. One of the strategies to combat MI and HF lies in the ability to accurately predict the onset of t...
Myocardial infarction (MI) and the ensuing heart failure (HF) remain the main cause of morbidity and mortality worldwide. One of the strategies to combat MI and HF lies in the ability to accurately predict the onset of these disorders. Alterations in mitochondrial homeostasis have been reported to be involved in the pathogenesis of various cardiovascular diseases (CVDs). In this regard, perturbations to mitochondrial dynamics leading to impaired clearance of dysfunctional mitochondria have been previously established to be a crucial trigger for MI/HF. In this study, we found that MI patients could be classified into three clusters based on the expression levels of mitophagy-related genes and consensus clustering. We identified a mitophagy-related diagnostic 5-genes signature for MI using support vector machines-Recursive Feature Elimination (SVM-RFE) and random forest, with the area under the ROC curve (AUC) value of the predictive model at 0.813. Additionally, the single-cell transcriptome and pseudo-time analyses showed that the mitoscore was significantly upregulated in macrophages, endothelial cells, pericytes, fibroblasts and monocytes in patients with ischemic cardiomyopathy, while sequestosome 1 (SQSTM1) exhibited remarkable increase in the infarcted (ICM) and non-infarcted (ICMN) myocardium samples dissected from the left ventricle compared with control samples. Lastly, through analysis of peripheral blood from MI patients, we found that the expression of SQSTM1 is positively correlated with troponin-T (P < 0.0001, R = 0.4195, R2 = 0.1759). Therefore, this study provides the rationale for a cell-specific mitophagy-related gene signature as an additional supporting diagnostic for CVDs.
3-methoxycatechol causes vasodilation likely via K channels: ex vivo, in silico docking and in vivo study.
Dias P, Salam R, Moravcová M … +6 more , Saadat S, Pourová J, Vopršalová M, Jirkovský E, Tebbens JD, Mladěnka P
Vascul Pharmacol · 2024 Sep · PMID 39159736 · Publisher ↗
Substituted catechols include both natural and synthetic compounds found in the environment and foods. Some of them are flavonoid metabolites formed by the gut microbiota which are absorbed afterwards. Our previous findi...
Substituted catechols include both natural and synthetic compounds found in the environment and foods. Some of them are flavonoid metabolites formed by the gut microbiota which are absorbed afterwards. Our previous findings showed that one of these metabolites, 4-methylcatechol, exerts potent vasorelaxant effects in rats. In the current study, we aimed at testing of its 22 structural congeners in order to find the most potent structure and to investigate the mechanism of action. 3-methoxycatechol (3-MOC), 4-ethylcatechol, 3,5-dichlorocatechol, 4-tert-butylcatechol, 4,5-dichlorocatechol, 3-fluorocatechol, 3-isopropylcatechol, 3-methylcatechol and the parent 4-methylcatechol exhibited high vasodilatory activities on isolated rat aortic rings with ECs ranging from ∼10 to 24 μM. Some significant sex-differences were found. The most potent compound, 3-MOC, relaxed also resistant mesenteric artery but not porcine coronary artery, and decreased arterial blood pressure in both male and female spontaneously hypertensive rats in vivo without affecting heart rate. It potentiated the vasodilation mediated by cAMP and cGMP, but did not impact L-type Ca-channels. By using two inhibitors, activation of voltage-gated potassium channels (K) was found to be involved in the mechanism of action. This was corroborated by docking analysis of 3-MOC with the K7.4 channel. None of the most active catechols decreased the viability of the A-10 rat embryonic thoracic aorta smooth muscle cell line. Our findings showed that various catechols can relax vascular smooth muscles and hence could provide templates for developing new antihypertensive vasodilator agents without affecting coronary circulation.
Association of serum 25-hydroxyvitamin D3 levels with carotid artery intima-media thickness and carotid atherosclerotic plaques in smokers.
Liu Y, Pei Y, Zhang S … +4 more , Du Z, Chen L, Yan X, Tian J
Vascul Pharmacol · 2024 Dec · PMID 39151593 · Publisher ↗
OBJECTIVE: This study explores the association of serum 25-hydroxyvitamin D3 (25(OH)D3) levels with carotid artery intima-media thickness (CIMT), and the presence of carotid atherosclerotic plaques in individuals with a...
OBJECTIVE: This study explores the association of serum 25-hydroxyvitamin D3 (25(OH)D3) levels with carotid artery intima-media thickness (CIMT), and the presence of carotid atherosclerotic plaques in individuals with a history of smoking. METHODS: A total of 469 patients suspected of having carotid atherosclerosis, aged 52 to 73 years with an average age of 65.26 ± 4.37 years, were recruited from the author's hospital from January 2023 to October 2023. All patients had a smoking history of nearly 5 years. Based on their serum 25(OH)D3 levels, they were divided into two groups: the normal group (serum level 30-50 ng/mL, n = 300) and the deficiency group (<30 ng/mL, n = 169). General details of the two patient groups were collected. Carotid artery ultrasound was employed to assess pulse wave velocity (PWV), carotid artery compliance coefficient (CC), and CIMT. Blood chemistry analysis measured serum lipid metabolism indicators including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HD-LC). The relationship between CIMT and each variable was analyzed through Pearson correlation, and logistic regression was used to identify risk factors influencing carotid artery plaque development. RESULTS: General patient information between the two groups showed no significant differences (P > 0.05). Patients in the 25(OH)D3 deficiency group exhibited elevated left and right PWV and CC compared to the 25(OH)D3 normal group (P < 0.05). The deficiency group exhibited larger CIMT and plaque area compared to the normal group (P < 0.05). Additionally, the deficiency group demonstrated higher levels of TC, LDL-C, and HD-LC compared to the normal group (P < 0.05). A moderate positive correlation was found between TC, LDL-C, and CIMT (P < 0.05), while a strong positive correlation existed between 25(OH)D3 and CIMT (P < 0.05). In smokers, the formation of carotid artery plaque was associated with factors such as patient age, CIMT, serum LDL-C, and 25(OH)D3 levels (P < 0.05). As age, CIMT, LDL-C levels increased, and 25(OH)D3 levels decreased, the risk of carotid plaques in smokers increased (P < 0.05). CONCLUSIONS: Smokers with lower 25(OH)D3 levels exhibit higher CIMT and more prominent carotid atherosclerotic plaques, indicating increased arterial stiffness and elevated cardiovascular risk. These findings demonstrate crucial implications that insufficient levels of vitamin D may potentially contribute to a higher risk of atherosclerosis among smokers.
Disease mechanisms and therapeutic targets in pulmonary hypertension: Key insights from the special issue of vascular pharmacology on pulmonary hypertension.
Wojciak-Stothard B, Gupte S, Bossone E
Vascul Pharmacol · 2024 Sep · PMID 39117158 · Publisher ↗
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