Journal of Cardiovascular Translational Research最新文献

Myocardial ischemia-reperfusion injury (IRI) is a major issue in cardiovascular medicine, marked by tissue damage from the restoration of blood flow after ischemia. Opioids, known for their pain-relieving properties, have emerged as potential cardioprotective agents in IRI. Recent research suggests opioids influence epigenetic mechanisms-such as histone modifications and non-coding RNAs (ncRNAs)-which are essential for regulating gene expression and cellular responses during myocardial IRI. This review delves into how opioids like remifentanil affect histone modifications, DNA methylation, and ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Remifentanil postconditioning (RPC) reduces apoptosis in cardiomyocytes through histone deacetylation, specifically downregulating histone deacetylase 3 (HDAC3). Similarly, opioids impact miRNAs such as miR- 206 - 3p and miR- 320 - 3p, and lncRNAs like TINCR and UCA1, which influence apoptosis, inflammation, and oxidative stress. Understanding these interactions highlights the potential for opioid-based therapies in mitigating IRI-induced myocardial damage.

Heart failure (HF) due to left ventricular (LV) dysfunction remains a major global health challenge, with inflammation driving its progression under chronic pressure overload, such as hypertension. This study explored the role of interleukin-22 (IL-22), a cytokine associated with tissue protection, in HF induced by transverse aortic constriction (TAC). IL-22 knockout (KO) mice exhibited exacerbated HF, marked by worsened LV hypertrophy, heightened inflammation, and impaired cardiac function compared to wild-type controls. Conversely, treatment with recombinant IL-22Fc improved LV function, reduced inflammatory cell infiltration, and alleviated cardiac remodeling and inflammation. These findings demonstrate that IL-22 plays a critical role in regulating inflammation and cardiac remodeling in pressure overload-induced HF. Targeting IL-22 may represent a promising therapeutic strategy to alleviate HF progression and associated pulmonary complications.

The magnesium depletion score (MDS) is considered a new valuable predictor of body magnesium status. This study aimed to explore the association between MDS and PAD among participants aged ≥ 40 years on the National Health and Nutrition Examination Survey in 1999-2004. Survey-weighted multivariable logistic regression and restricted cubic spline models were used to assess the association between MDS and PAD. Survey-weighted multivariable logistic regression showed a significant positive association between MDS and the prevalence of PAD. For each unit increase in MDS, the risk of PAD increased by 24%. Compared to individuals with MDS = 0, those with MDS ≥ 3 had a 95% higher risk of PAD. Restricted triple spline analysis showed a linear dose-response relationship between MDS and PAD risk. Subgroup analysis indicated that this positive association was stronger in individuals aged > 60 years. Numerous future longitudinal cohort studies are required to validate our findings.

Pulmonary arterial hypertension (PAH) poses a challenge due to limited curative options and ineffective treatments. Mesenchymal stem cell (MSC) therapy has emerged as a potential intervention for PAH. This study delved into the therapeutic potential and molecular mechanisms underlying MSC-based apelin gene therapy in PAH rats induced by monocrotaline (MCT). Wharton's jelly-derived MSCs transfected with pcSLenti-APLN were utilized as therapeutic agents. Transplanted MSCs successfully homed to the lung tissue of rats and sustained survival for at least three weeks. MSC-mediated apelin gene therapy effectively reduced pulmonary artery pressure, mitigated pulmonary vascular remodeling, and modulated apoptosis in MCT-induced PAH rats. Furthermore, the phosphatidylinositol 3-kinase (PI3K)/AKT/endothelial nitric oxide synthase (eNOS) and ERK1/2 signaling pathways were involved in the therapeutic effects. Meanwhile, Apelin-MSCs also regulated MCT-induced changes of Bax and Bcl-2 in the lung lobes and pulmonary arterioles. MSC-based apelin gene therapy could be considered a possible therapeutic strategy for PAH.

Heart failure (HF) treatment remains one of the major challenges in cardiovascular disease management, and its pathogenesis requires further exploration. Cardiac metabolic remodeling is of great significance as a key pathological process in the progression of HF. The complex alterations of metabolic substrates and associated enzymes in mitochondria create a vicious cycle in HF. These changes lead to increased reactive oxygen species, altered mitochondrial Ca²⁺ handling, and the accumulation of fatty acids, contributing to impaired mitochondrial function. In this context, mitophagy plays a significant role in clearing damaged mitochondria, thereby maintaining mitochondrial function and preserving cardiac function by modulating metabolic remodeling in HF. This article aims to explore the role of mitophagy in cardiac metabolic remodeling in HF, especially in obesity cardiomyopathy, diabetic cardiomyopathy, and excessive afterload-induced heart failure, thoroughly analyze its molecular mechanisms, and review the therapeutic strategies and prospects based on the regulation of mitophagy.

Translational models for obstructive coronary artery disease are lacking. We aimed to develop a porcine model for obstructive coronary stenosis induced by bioresorbable stent (BRS) implantation in hypercholesterolemic proprotein convertase subtilisin/kexin-9 (PCSK9) minipigs. Fifteen hypercholesterolemic PCSK9 minipigs were randomized to percutaneous coronary intervention with Magmaris, Absorb or Desolve BRS. Optical coherence tomography (OCT) scans were performed at baseline and 6-months followed by histology. Matched OCT analysis showed minimal lumen area decreased from 7.62 ± 1.54 mm² at baseline to 2.12 ± 0.92 mm² at follow-up in the Magmaris group, from 6.99 ± 1.49 mm² to 3.07 ± 1.52 mm² in the Absorb group, and from 6.05 ± 1.11 mm² to 2.65 ± 0.93 mm² in the Desolve group. Histologic examination revealed advanced human-like stenosis. BRS implantation in hypercholesterolemic PCSK9 minipigs induced human-like stenoses and may serve as a feasible preclinical model for obstructive coronary artery disease.

Lipoxygenases (LOXs) are a family of dioxygenases that catalyze the peroxidation of polyunsaturated fatty acids, such as linoleic acid and arachidonic acid, initiating the synthesis of bioactive lipid mediators. The LOX-mediated production of these bioactive molecules in various cell types plays a critical role in the pathophysiology of cardiovascular diseases, including atherosclerosis, hypertension, and myocardial ischemia-reperfusion injury. In this review, we summarize the roles of LOXs and their products in different cardiovascular cells and conditions, offering valuable insights may contribute to the development of novel therapeutic strategies for cardiovascular diseases.

Heart failure (HF) is a clinical syndrome caused by structural or functional abnormalities in heart. Egr2 has been reported to be protective for multiple diseases, but its effect on HF remains unknown. The present study intended to investigate the potential role of Egr2 in HF and its possible downstream effectors. High Egr2 expression in heart was observed in HF mice. Egr2 knockdown alleviated cardiac damage and function in HF mice. Egr2 knockdown inhibited myocardial inflammation and apoptosis both in vivo and in vitro. Egr2 inhibited Acot1 transcription expression via directly binding to its promoter. Acot1 overexpression reduced Lipopolysaccharide (LPS)-induced cardiomyocyte inflammation and apoptosis. Functional rescue experiments revealed that Acot1 reversed the effects of Egr2 on LPS-induced cell apoptosis and inflammation. Overall, Egr2 knockdown might ameliorate HF by inhibiting inflammation and apoptosis in cardiomyocytes by targeting Acot1. This study might provide evidence to better understand the molecular mechanisms of HF pathogenesis.

Cardiomyocyte hypertrophy is a key remodeling response to cardiac stress and an independent risk factor for heart failure. However, the molecular mechanism of cardiomyocyte hypertrophy is not yet fully understood. We here found Polo-like kinase 1 (PLK1) was crucial in regulating endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy. Notably, PLK1 expression was significantly elevated in ET-1-induced hypertrophic cardiomyocytes and pressure overload-induced hypertrophic cardiac tissue. Knocking down Plk1 reduced the cell size of hypertrophic cardiomyocytes and suppressed the expression of hypertrophic markers, including ANP, BNP and β-MHC. The PLK1 inhibitor BI2536 had similar effects on hypertrophic cardiomyocytes. Mechanistically, the ERK1/2 pathway was identified as the key downstream pathway mediating the effects of PLK1 on ET-1-induced cardiomyocyte hypertrophy. Finally, the deficiency of PLK1 attenuated the hypertrophy of hiPSC-CMs. In summary, our study revealed that PLK1 regulates ET-1-induced cardiomyocyte hypertrophy through the ERK1/2 pathway, providing insights into the pathogenesis and potential therapies for pathological cardiac hypertrophy.

Cardio-Kidney-Metabolic (CKM) Syndrome involves metabolic, kidney, and cardiovascular dysfunction, disproportionately affecting disadvantaged groups. Its staging (0-4) highlights the importance of early intervention. While current management targets hypertension, heart failure, dyslipidemia, and diabetes, RNA-based therapies offer innovative solutions by addressing molecular mechanisms of CKM Syndrome. Emerging RNA treatments, including antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), show promise in slowing disease progression across CKM stages. For example, ASOs and siRNAs targeting ApoC-III and ANGPTL3 reduce triglycerides and LDL cholesterol, while siRNAs improve blood pressure control by targeting the renin-angiotensin-aldosterone system. Obesity treatments leveraging miRNAs and circRNAs tackle a key CKM risk factor. In heart failure and diabetes, RNA-based therapies improve cardiac function and glucose control, while early kidney disease trials show potential for RNAi in acute injury. Further research is essential to refine these therapies and ensure equitable access.