Journal of Cardiovascular Pharmacology最新文献

Abstract: Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive lung disease marked by extracellular matrix deposition, oxidative stress, and profound microvascular remodeling. Endothelial dysfunction, particularly through endothelial-to-mesenchymal transition (EndMT), has been implicated in fibrotic progression but remains insufficiently characterized. In this study, human pulmonary microvascular endothelial cells were exposed to 5% serum from patients with IPF or healthy donors to model disease-associated vascular alterations. IPF serum stimulated a robust increase in reactive oxygen species (ROS) production and proliferation, concomitant with downregulation of endothelial markers (von Willebrand factor, CD31) and upregulation of mesenchymal markers (α-smooth muscle actin, collagen I), consistent with EndMT induction. Notably, pharmacological inhibition of NADPH oxidase (NOX) with diphenyleneiodonium markedly attenuated ROS generation, phenotypic switching, and junctional disruption observed under IPF serum exposure. Similarly, inhibition of protein kinase C (PKC) by chelerythrine suppressed ROS production and proliferative responses, implicating PKC-dependent pathways in ROS-mediated endothelial injury. Immunofluorescence analyses confirmed structural reorganization, revealing loss of endothelial junctional integrity and accumulation of mesenchymal proteins, both reversed by NOX inhibition. Together, these findings establish IPF serum-derived factors as potent drivers of endothelial oxidative stress and EndMT through NOX- and PKC-dependent mechanisms. Targeting these redox-sensitive pathways may represent a promising therapeutic strategy to mitigate vascular dysfunction, tissue remodeling, and disease progression in IPF.

Abstract: Triptolide (TP) is widely used clinically for multiple diseases, but its cardiotoxicity significantly limits its clinical applications. The underlying mechanisms of its cardiotoxicity are still unclear. Mitochondria are crucial for cellular survival and function. Here, we found that TP induced mitochondrial dysfunction and apoptosis of cardiomyocytes, which might be the key process underlying TP-induced cardiotoxicity. Moreover, the expression of prohibitin1 (PHB1) was significantly decreased after TP treatment in a time-dependent manner. Overexpression of PHB1 alleviated mitochondrial dysfunction and inhibited apoptosis of cardiomyocytes after TP treatment. Mechanistically, PHB1 might regulate mitochondrial dynamics, which maintain normal mitochondrial function. Based on the above results, PHB1 might be a potential therapeutic target for TP-induced cardiotoxicity.

Abstract: Fulminant myocarditis (FM) is a critical condition with high mortality. Interleukin-1 (IL-1) is a key mediator of myocardial inflammation. We describe the case of a 19-year-old man with FM, hemodynamic deterioration refractory to standard treatment, and a marked systemic inflammatory response. The introduction of anakinra, an IL-1 receptor antagonist, led to rapid clinical, hemodynamic, and laboratory improvement. A literature review identifies other cases of severe/fulminant myocarditis with hyperinflammation that benefited from IL-1 blockade, despite heterogeneous etiologies. These data suggest that anakinra could be a valuable rescue therapeutic option in selected patients with FM and hyperinflammation. Randomized trials are needed to confirm the role of IL-1 blockade in this high-risk population, focusing on the pharmacology of the immune response.

Abstract: This study investigates the cardioprotective potential of soluble guanylate cyclase (sGC) and its α1 subunit in myocardial ischemia/reperfusion (I/R) injury, along with the underlying mechanisms. We used a model involving Sprague Dawley rats undergoing left coronary artery I/R, complemented by H9c2 cell cultures in an anaerobic environment to simulate I/R conditions in vitro. Both loss- and gain-of-function approaches were applied to assess the role of sGC and its α1 subunit in myocardial I/R injury. Immunofluorescence microscopy, western blotting, and RT-PCR were employed to examine how sGC and its α1 subunit influence oxidative stress and apoptosis. Our results showed that sGC and its α1 subunit were associated with reduced I/R injury severity in both in vitro and in vivo settings. Overexpression of sGC decreased cardiomyocyte apoptosis and maintained mitochondrial function during I/R, whereas sGC silencing heightened oxidative stress and apoptosis. In addition, pharmacological modulation of sGC affected signaling in the peroxisome proliferator-activated receptor-γ coactivator-1α/uncoupling protein 2 pathway. These findings demonstrate the crucial role of sGC and its α1 subunit in protecting against cardiac injury during I/R, suggesting that sGC-targeted therapies could offer promising strategies for managing myocardial damage associated with I/R injury.

Abstract: Diabetic cardiomyopathy (DCM), a global cardiovascular complication of diabetes, is characterized by concurrent diastolic and systolic ventricular dysfunction that progressively leads to heart failure, arrhythmias, and cardiogenic shock. Despite advancements in modern therapeutics, DCM continues to exhibit high mortality rates, underscoring the critical need for novel preventive and therapeutic strategies. In recent years, traditional Chinese medicine (TCM) has gained prominence in DCM management due to its established safety profile and emerging evidence of clinical efficacy. Current research focuses on elucidating TCM's multitarget mechanisms, particularly its regulatory effects on metabolic homeostasis, oxidative stress, and inflammatory pathways-key pathological processes in DCM progression. This review systematically investigates the latest advancements in TCM for DCM management through 3 principal dimensions: First, it synthesizes the etiological understanding of DCM from both TCM theory and modern medical perspectives, highlighting their complementary mechanisms in disease pathogenesis. Second, it critically evaluates the therapeutic potential of clinically validated Chinese herbal agents, focusing on their bioactive compounds that target myocardial energy metabolism and oxidative stress pathways. Third, it systematically summarizes evidence-based TCM therapeutic strategies. By consolidating existing evidence, this review aims to provide a rigorous assessment of TCM's clinical value in DCM management, while proposing standardized frameworks to facilitate deeper integration of TCM principles with evidence-based cardiology practice.

Injectable PCSK9 inhibitors effectively lower LDL-C levels in patients with hypercholesterolemia; however, their high cost and requirement for parenteral administration limit their widespread use. Oral PCSK9 inhibitors have emerged as a convenient alternative. This review and meta-analysis of the literature evaluate the effectiveness and safety of oral PCSK9 inhibitor treatment for adults with hypercholesterolemia. PubMed, Embase, Cochrane CENTRAL, and Scopus were searched through September 2025 for randomized controlled trials comparing oral PCSK9 inhibitors with placebo. The primary outcome was percentage change in LDL-C, with secondary lipid and safety outcomes. We used Cochrane RoB 2.0 tool to assess risk of bias, and pooled estimates were calculated using a random-effects model. Certainty of evidence was evaluated with GRADE. From 1,253 records, three trials were included. Participants were mostly male, aged 61-65 years, with elevated baseline LDL-C. Oral PCSK9 inhibitors significantly reduced LDL-C and ApoB in a dose-dependent manner and achieved modest reductions in triglycerides (MD -6.56 mg/dL; 95% CI: -12.30 to -0.83) and total cholesterol (MD -25.25 mg/dL; 95% CI: -30.67 to -19.83). Effects on lipoprotein(a) were inconsistent. Adverse events (RR 1.06; 95% CI: 0.91-1.23) and serious adverse events (RR 1.32; 95% CI: 0.41-4.26) were comparable to placebo. According to our review, oral PCSK9 inhibitors are a promising therapeutic option for treating hypercholesterolemia due to their potent lipid-lowering effects and an overall favorable safety profile. However, more trials are needed to confirm their impact on cardiovascular outcomes.