J Cardiovasc Transl Res
· 2026 Jun · PMID 42234053
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Ferroptosis is a critical contributor to cardiomyocyte injury in acute myocardial infarction (AMI). This study aimed to identify key ferroptosis-associated genes and elucidate their roles in AMI. Transcriptomic datasets...Ferroptosis is a critical contributor to cardiomyocyte injury in acute myocardial infarction (AMI). This study aimed to identify key ferroptosis-associated genes and elucidate their roles in AMI. Transcriptomic datasets from AMI patients and healthy controls were analyzed to identify differentially expressed genes (DEGs). The role of the solute carrier family 11 member 1 (SLC11A1) was validated in vitro using a hypoxia/reoxygenation (H/R) model in H9c2 cardiomyocytes and in vivo using a murine AMI model. SLC11A1 expression was elevated in H/R-treated cardiomyocytes and infarcted murine hearts. SLC11A1 silencing reduced infarct size and improved cardiac function, and suppressed ferroptosis. Mechanistically, SLC11A1 led to the transcriptional suppression of glutathione peroxidase 4 (GPX4) mediated by the transcription factor specificity protein 1 (Sp1). This study identifies the SLC11A1-Sp1-GPX4 axis as a pivotal transcriptional regulator pathway driving ferroptosis in AMI. These findings highlight SLC11A1 as a promising therapeutic target in AMI.
Kang YX, Hu Y, Sun XT
… +11 more, Fan XB, Li AL, Shang WY, Jia YF, Zhao YX, Wei MM, Wang TQ, Zhang Z, Zhu BY, Liang YC, Zhang JP
J Cardiovasc Transl Res
· 2026 May · PMID 42209899
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Mitochondrial dysfunction has long been recognized as a central driver of heart failure (HF) pathogenesis, and emerging evidence highlights that impaired mitochondrial communication, rather than merely energy metabolism...Mitochondrial dysfunction has long been recognized as a central driver of heart failure (HF) pathogenesis, and emerging evidence highlights that impaired mitochondrial communication, rather than merely energy metabolism dysfunction, plays a pivotal role in the initiation and progression of HF. These communication networks are critical for maintaining cardiac metabolic homeostasis, and their disruption in HF leads to dysregulated energy metabolism, oxidative stress, lipotoxicity, and impaired cardiomyocyte function. This review examines the functional interactions between mitochondria and these organelles in HF, with particular attention to phenotype-specific differences between HF with preserved ejection fraction and HF with reduced ejection fraction. Finally, we summarize current and emerging therapeutic strategies targeting mitochondrial communication, highlighting the potential for phenotype-tailored interventions that restore organelle interplay and metabolic balance in HF.
J Cardiovasc Transl Res
· 2026 May · PMID 42201566
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Cardiovascular diseases (CVDs), including coronary artery disease, heart failure, arrhythmias, hypertension, and cardiomyopathy, promote disease progression in part through profound disturbances in cardiomyocyte metaboli...Cardiovascular diseases (CVDs), including coronary artery disease, heart failure, arrhythmias, hypertension, and cardiomyopathy, promote disease progression in part through profound disturbances in cardiomyocyte metabolism. These disorders are characterized by abnormal lipid and glucose metabolism and dysfunction of key metabolic regulatory systems, including fatty acid transport proteins and the AMPK/eNOS signaling axis. Exercise training regulates substrate selection and activates essential metabolic pathways, including PGC-1α and PPAR-α, thereby improving myocardial energy homeostasis and limiting cardiac injury. This review summarizes the mechanisms by which exercise modulates myocardial metabolism to delay or reverse disease progression across multiple forms of CVDs. Current evidence indicates that distinct cardiovascular pathologies exhibit unique metabolic abnormalities, suggesting that exercise interventions may exert disease-specific therapeutic effects by selectively targeting altered metabolic pathways.
J Cardiovasc Transl Res
· 2026 May · PMID 42192039
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Post traumatic stress disorder (PTSD) is defined as a mental health condition that occurs after experiencing a traumatic event. Patients diagnosed with PTSD have a 30-45% increase in cardiovascular disease (CVD) risk or...Post traumatic stress disorder (PTSD) is defined as a mental health condition that occurs after experiencing a traumatic event. Patients diagnosed with PTSD have a 30-45% increase in cardiovascular disease (CVD) risk or cardiac-specific mortality even after adjusting for depression, demographic, clinical (e.g., age, blood pressure, body mass index (BMI), and tobacco use), and psychosocial factors. With this, the lifetime prevalence of PTSD has a notable sex disparity: women have a prevalence of approximately 10%, compared to 4% in men. Mechanisms explaining the increased risk of CVD in PTSD patients is unclear, leaving this patient population vulnerable as well as placing a substantial economic burden on the United States healthcare system. In this review, we will discuss the effect of PTSD on cardiovascular physiology, with an emphasis on sex differences, mechanisms of inflammation, and impaired ANS responses. In addition, we will summarize current and experimental therapeutics for PTSD that may help mitigate the risk of CVD.
Xie J, Gemeinhardt O, Bettink S
… +5 more, Hauptmann R, Schannor M, Loechel M, Speck U, Haase T
J Cardiovasc Transl Res
· 2026 May · PMID 42191941
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The porcine in-stent stenosis model has been essential for developing drug-coated devices but does not replicate the hyperlipidemic, pro-atherogenic conditions driving neoatherosclerosis. We aimed to establish a practica...The porcine in-stent stenosis model has been essential for developing drug-coated devices but does not replicate the hyperlipidemic, pro-atherogenic conditions driving neoatherosclerosis. We aimed to establish a practical porcine model for testing endovascular therapies targeting neoatherosclerosis. Juvenile pigs were fed a high-fat, nicotine-supplemented diet (HFDN). After two weeks, bare-metal stents were implanted in coronary and peripheral arteries; controls received a standard diet. Four weeks later, stented, and non-stented artery segments were analyzed. HFDN feeding induced elevated serum LDL and cotinine. At follow-up, in-stent late lumen loss was significantly greater in peripheral arteries (A. iliaca: 2.3 ± 0.6 vs. 1.1 ± 0.5 mm; A. femoralis: 3.4 ± 1.2 vs. 2.0 ± 0.4 mm), but not coronary arteries. HFDN-fed pigs showed distinct signs of early neoatherosclerosis, including peri-strut foam cell accumulations and atheroma formation. Elemental imaging and chemical analysis confirmed increased calcium phosphate deposition in arteries of HFDN-fed pigs. This straightforward protocol enables testing of devices aimed at preventing or treating neoatherosclerosis.
J Cardiovasc Transl Res
· 2026 May · PMID 42156597
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Pathological cardiac hypertrophy is a key precursor to heart failure. The role of Xanthatin in this process was unknown. This study aimed to investigate its effects and molecular target. A mouse model of Ang II-induced h...Pathological cardiac hypertrophy is a key precursor to heart failure. The role of Xanthatin in this process was unknown. This study aimed to investigate its effects and molecular target. A mouse model of Ang II-induced hypertrophy was used. Xanthatin's effects were assessed by echocardiography and histology. Cardiac-specific overexpression or knockdown of CREB5 was performed using AAV9-cTNT vectors during Ang II and Xanthatin co-treatment to validate its functional role. Xanthatin treatment significantly alleviated Ang II-induced cardiac hypertrophy, oxidative stress, fibrosis, and inflammation. Crucially, cardiac-specific overexpression of CREB5 markedly attenuated these protective effects of Xanthatin. Conversely, cardiac-specific knockdown of CREB5 synergized with Xanthatin, further enhancing its suppressive actions on all pathological hallmarks. Xanthatin is a potent inhibitor of Ang II-induced cardiac hypertrophy, and its protective effect is mediated through the suppression of CREB5 signaling. This identifies the Xanthatin-CREB5 axis as a novel and promising therapeutic target for pathological cardiac remodeling.
Sindledecker AM, Nabeel Y, Palladino O
… +1 more, Frazee LA
J Cardiovasc Transl Res
· 2026 May · PMID 42156590
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Correction of iron deficiency (ID) with intravenous iron among patients with heart failure (HF) may improve outcomes but is rarely assessed in real-world studies. Hospital admission for decompensated HF presents an oppor...Correction of iron deficiency (ID) with intravenous iron among patients with heart failure (HF) may improve outcomes but is rarely assessed in real-world studies. Hospital admission for decompensated HF presents an opportunity to identify patients for treatment of ID. Of 2,275 patient admissions for decompensated HF, iron studies were available for 526 (23.1%) and ID was identified in 332 (63.1%) patients. Iron replacement was oral in 241 (10.6%) or intravenous in 285 (12.5%) with 132 (46.3%) patients receiving treatment during the admission. Anemia, chronic kidney disease stage 3 (CKD3), and low mean corpuscular volume (MCV) were associated with a higher odds of iron study availability while age was associated with lower odds. Frequency of assessment of ID in HF patients remains low. Predictors of iron status assessment indicate that factors related to anemia rather than HF are likely responsible for iron status assessment among these patients.
Langmuur SJJ, Amesz JH, Alipour Symakani RS
… +6 more, Veen KM, Meuwese CL, Bogers AJJC, de Groot NMS, Manintveld OC, Taverne YJHJ
J Cardiovasc Transl Res
· 2026 May · PMID 42115510
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This study aimed to compare baseline biomechanical contractile properties between right (RV) and left ventricular (LV) human living myocardial slices (LMS) and explore the effect of dobutamine, noradrenaline, adrenaline,...This study aimed to compare baseline biomechanical contractile properties between right (RV) and left ventricular (LV) human living myocardial slices (LMS) and explore the effect of dobutamine, noradrenaline, adrenaline, levosimendan and enoximone in both ventricles. Sixty-three slices (33 RV, 30 LV) were produced from 5 explanted hearts. At baseline, RV LMS had a higher maximum contraction force, shorter contraction duration, time to peak and time to relaxation, steeper dF/dt and a larger peak area than LV LMS. Dobutamine administration had a larger effect in RV than LV LMS. Spontaneous, irregular contractions were observed after noradrenaline, adrenaline and dobutamine administration. In conclusion, RV LMS showed a stronger contraction with higher contraction velocity as compared to LV LMS and exhibited a greater response to dobutamine. These findings contribute to the understanding of the RV physiology as a separate entity, advocating for a different approach in treating RV or LV dysfunction.
Li Y, Chen Y, Yang J
… +4 more, Mai B, Chen J, Wang J, Xie S
J Cardiovasc Transl Res
· 2026 May · PMID 42113345
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Adverse cardiac remodeling after myocardial infarction (MI) is a major cause of heart failure. Macrophage polarization plays a pivotal role in this process. Siglec-E, an immunoregulatory molecule expressed on myeloid cel...Adverse cardiac remodeling after myocardial infarction (MI) is a major cause of heart failure. Macrophage polarization plays a pivotal role in this process. Siglec-E, an immunoregulatory molecule expressed on myeloid cells, modulates macrophage function, yet its specific role in post-MI cardiac remodeling remains unknown. Elucidating this role may reveal novel therapeutic strategies and provide critical safety insights for Siglec-E-targeted anticancer therapies. Siglec-9 (the human homolog of Siglec-E) expression was first identified in GEO datasets and validated by flow cytometry in a human cohort (AMI,controls,and CCS). Siglec-E expression was then examined in murine models of MI. To assess its functional role, Siglec-E⁻/⁻ and wild-type mice were subjected to permanent coronary artery ligation. Cardiac remodeling was evaluated by echocardiography and histopathological examination. Immune cell profiles, macrophage polarization, and inflammatory gene expression were analyzed by flow cytometry,immunofluorescence, and qPCR. Finally, macrophage depletion and adoptive transfer studies were performed to establish causality. Siglec-9/E expression was upregulated in monocytes/macrophages after MI in human and mice. Compared to WT controls, Siglec-E⁻/⁻ mice exhibited worsened survival, impaired cardiac function (reduced left ventricular ejection fraction and fractional shortening, increased ventricular volumes), larger infarct size, exacerbated fibrosis, and enhanced cardiomyocyte apoptosis after MI. Mechanistically, Siglec-E deficiency skewed cardiac macrophages toward a pro-inflammatory M1 phenotype, without affecting neutrophil recruitment. Macrophage depletion abolished the adverse phenotype in Siglec-E⁻/⁻ mice. Adoptive transfer of wild-type macrophages attenuated cardiac injury, whereas transfer of Siglec-E⁻/⁻ macrophages exacerbated adverse remodeling. Siglec-E is a key regulator of post-MI cardiac remodeling by restraining pro-inflammatory M1 macrophage polarization. Targeting macrophage Siglec-E signaling may represent a promising therapeutic strategy for heart failure.
El-Menyar A, Khan NA, Abid AR
… +2 more, Elmenyar E, Al-Thani H
J Cardiovasc Transl Res
· 2026 Apr · PMID 42043702
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Brain-heart interactions have garnered considerable interest in the landscape of traumatic brain injury (TBI). This scoping review focused on bradycardia caused by high intracranial pressure (ICP), brainstem injury, auto...Brain-heart interactions have garnered considerable interest in the landscape of traumatic brain injury (TBI). This scoping review focused on bradycardia caused by high intracranial pressure (ICP), brainstem injury, autonomic imbalance, hypothalamic-pituitary-adrenal axis disruption, or massive bleeding. The latter condition is attributed to a physiological phenomenon called relative bradycardia (RB). True bradycardia results from underlying physiological or pathological cardiac disorders, whereas RB has different definitions and implications in medical and surgical settings. The former reflects pulse-temperature dissociation, while the latter reflects pulse-pressure dissociation. However, it can reflect an abnormal neurological response called the Cushing reflex. Therefore, bradycardia may indicate imminent shock after TBI associated with torso injuries or high ICP following severe isolated TBI. RB is underrecognized and underappreciated in emergency settings. This review investigated whether RB affects patient survival and neurological function. Physicians should approach patients presenting with RB with a high index of suspicion and timely management.
Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation and redox imbalance, has recently garnered significant attention for its critical role in the pathogenesis of cardiovascular...Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation and redox imbalance, has recently garnered significant attention for its critical role in the pathogenesis of cardiovascular diseases (CVDs). Accumulating evidence suggests that ferroptosis contributes to a range of cardiovascular pathologies by disturbing iron homeostasis, promoting oxidative stress, and impairing mitochondrial function. Traditional Chinese medicine (TCM), with its multi-component and multi-target properties and relatively low toxicity, has shown unique therapeutic potential in modulating ferroptosis-related pathways. This review provides a comprehensive summary of the current understanding of ferroptosis in CVDs and highlights the mechanisms by which TCM and its bioactive constituents influence ferroptosis. We further discuss the therapeutic implications and translational challenges, aiming to provide novel insights into ferroptosis-targeted interventions for CVDs from the perspective of TCM.
Atherosclerosis is the major pathological basis of cardiovascular diseases, characterized by chronic inflammation and disturbed glucose and lipid metabolism. Despite the widespread use of statins, the global clinical bur...Atherosclerosis is the major pathological basis of cardiovascular diseases, characterized by chronic inflammation and disturbed glucose and lipid metabolism. Despite the widespread use of statins, the global clinical burden continues to rise, and effective therapeutic strategies remain limited. As the "second genome," gut microbiota participates in the progression of atherosclerosis by regulating host glucose and lipid metabolism, inflammatory responses, and metabolite production. Natural plant components exert multiple effects, including regulating glucose and lipid metabolism, modulating gut microbiota, and anti-inflammatory activity, showing unique advantages in the prevention and treatment of atherosclerosis. This review summarizes the mechanisms underlying the anti-atherosclerotic effects of gut microbiota via regulating glucose and lipid metabolism, as well as the role of natural plant components in intervening disease progression by remodeling intestinal microecology and reducing pro-atherogenic metabolites. It provides a theoretical basis for novel therapeutic strategies targeting gut microbiota and the clinical application of plant components.
Zulkefli SB, Mohamad F, Nasir NAA
… +2 more, Shuid AN, Azme N
J Cardiovasc Transl Res
· 2026 Mar · PMID 41913031
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Atherosclerosis in postmenopausal women is a significant cardiovascular complication that is caused by estrogen deficiency, leading to increased inflammation and oxidative stress, and dysregulated lipid metabolism. The r...Atherosclerosis in postmenopausal women is a significant cardiovascular complication that is caused by estrogen deficiency, leading to increased inflammation and oxidative stress, and dysregulated lipid metabolism. The review summarizes the evidence gathered in ovariectomized mice models in order to determine mechanistic associations between different pharmacological therapeutic strategies and their impact on the progression of atherosclerosis in postmenopausal conditions. This review builds on an upstream hormonal signaling framework model of estrogen receptor-mediated pathways and the three main downstream mechanistic pillars: lipid handling, inflammatory and oxidative stress pathways, and endothelial homeostasis. In this framework context, downstream consequence mechanisms, including PCSK9 regulation and ferroptosis, are analyzed along with emerging evidence linking estrogen deficiency to modulation of the gut microbiota. The evidence shows the complex interconnections among hormonal, metabolic, and vascular processes underlying postmenopausal atherosclerosis, providing a translational framework for applying therapeutic interventions.
Li Q, Wang J, Jiang Y
… +8 more, Wang F, Liu M, Yang D, Yan X, Wang Y, Du H, You Q, Liu K
J Cardiovasc Transl Res
· 2026 Mar · PMID 41894055
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Ischemic heart disease, as one of the major causes of morbidity worldwide, there is no effective therapy for preventing myocardial ischemia-reperfusion injury (MIRI). Baicalin, a flavonoid glycoside extracted from the Sc...Ischemic heart disease, as one of the major causes of morbidity worldwide, there is no effective therapy for preventing myocardial ischemia-reperfusion injury (MIRI). Baicalin, a flavonoid glycoside extracted from the Scutellaria baicalensis Georgi, yet its effects in MIRI remain unclear. In the study, pretreatment with Baicalin (100 mg/kg, i.p.) markedly alleviated I/R-induced cardiac dysfunction, as shown by reduced serum lactate dehydrogenase (LDH), creatine kinase (CK), and myocardial infarction. Baicalin also improved cardiomyocyte survival by increasing Bcl-2 and decreasing Bax and caspase-3/9 levels. In addition, Baicalin suppressed oxidative stress by reducing malondialdehyde (MDA) while elevating glutathione (GSH) and superoxide dismutase (SOD) levels. Moreover, Baicalin inhibited the STING, NLRP3, cleaved caspase-1, IL-18, and IL-1β expression in vivo and in vitro. Crucially, amidobenzimidazole (ABZI), a STING agonist, reversed the cardioprotective effects of Baicalin. Collectively, these findings demonstrated that Baicalin exerted cardioprotective effects by attenuating apoptosis and oxidative stress through suppression of STING/NLRP3 activation.
Zhang Y, Yang W, Zhang J
… +7 more, A J, Shen J, Qi Z, Qian J, Sun A, Ge J, Zhang S
J Cardiovasc Transl Res
· 2026 Mar · PMID 41874920
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Phenylacetylglutamine (PAGln), a gut microbiota-derived metabolite, is associated with enhanced thrombosis. However, its impact on endothelial function and angiogenesis remains unclear. A murine hindlimb ischemia model w...Phenylacetylglutamine (PAGln), a gut microbiota-derived metabolite, is associated with enhanced thrombosis. However, its impact on endothelial function and angiogenesis remains unclear. A murine hindlimb ischemia model was used to assess perfusion recovery. Human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation were evaluated in vitro. Gene set enrichment analysis (GSEA) was performed for pathway enrichment analyses. Furthermore, glycolytic flux and enzyme expression were measured. Lentiviral lactate dehydrogenase A (LDHA) overexpression was performed both in vitro and in vivo. Elevated PAGln impaired blood flow recovery and inhibited HUVEC proliferation, migration and tube formation. β-receptor blocker zenidolol was able to reverse the adverse effects. PAGln downregulated glycolytic pathways, reduced proton efflux, and suppressed LDHA expression and lactate production. LDHA overexpression rescued PAGln-induced angiogenic impairment. The gut metabolite PAGln may suppress angiogenesis of HUVEC by targeting the β-receptors, subseqeuently inhibiting LDHA expression.