Cardiovascular Drugs and Therapy最新文献

Vascular calcification (VC), a pathological hallmark of advanced atherosclerosis, exerts a profound impact on arterial stiffness and the incidence of cardiovascular disease. Its development involves not only actively regulated biological processes but also passive mineral deposition and is particularly prevalent in patients with diabetes, chronic kidney disease, and endocrine disorders. Although conventional therapies-such as phosphate binders, calcium channel blockers, bisphosphonates, and endovascular interventions-form the current clinical foundation, they remain inadequate for preventing early VC or reversing established lesions. This review systematically summarizes advances in both standard strategies and emerging therapies. Recent studies have highlighted several breakthrough approaches: nanotechnology-based delivery systems, optimized agents such as SNF472 and GLP-1 receptor agonists, and bioactive constituents from traditional Chinese medicine (e.g., ginsenosides, chelerythrine), all of which target distinct calcification pathways. In addition, dietary interventions and lifestyle modification show preventive value. Progress in multi-omics technologies continues to uncover new molecular mechanisms and therapeutic targets, guiding precision medicine. By integrating mechanistic insights with novel therapeutic paradigms, this review aims to facilitate the development of personalized management strategies and ultimately improve cardiovascular outcomes in high-risk populations.

Heart failure (HF) is a progressive clinical syndrome characterized by structural and functional cardiac impairment, leading to reduced cardiac output, hemodynamic instability, and high morbidity and mortality. Emerging evidence highlights calcitonin gene-related peptide (CGRP) as a crucial regulator of cardiovascular homeostasis, owing to its potent vasodilatory, cardioprotective, anti-inflammatory, and antifibrotic properties. CGRP, predominantly synthesized by sensory neurons, maintains vascular tone, enhances myocardial perfusion, and counteracts maladaptive neurohormonal activation involving the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS). In early HF, elevated CGRP levels provide compensatory benefits by reducing afterload, preserving endothelial integrity, and mitigating ventricular remodeling. However, progressive disease stages are characterized by CGRP depletion, receptor downregulation, and impaired signaling, which diminish its protective effects and contribute to pathological fibrosis, hypertrophy, and disruption of the extracellular matrix. Therapeutic strategies targeting CGRP signaling, including peptide agonists, stable analogues such as SAX, gene-based therapies enhancing endogenous CGRP expression, receptor modulators, and TRPV1-induced release stimulators, show promising results in preclinical studies and early-phase clinical studies, demonstrating improved cardiac output, reduced infarct size, and preserved ventricular function. Patients with early-to-mid HF (NYHA I-III), HFpEF with endothelial dysfunction, and hypertension-or-ischemia-driven HF may particularly benefit from CGRP-directed therapies. Conversely, the widespread use of CGRP antagonists for migraine therapy necessitates careful cardiovascular safety evaluation, especially in HF populations. Ongoing clinical trials are exploring CGRP-based interventions are diagnostic biomarkers, personalized therapeutic agents, and disease-modifying treatments. This review consolidates current insights into the physiological and pathophysiological roles of CGRP in HF, evaluates therapeutic opportunities and safety concerns, and discusses future directions, including patient stratification, biomarker-guided precision medicine, and combination regimens. Targeting CGRP pathways holds significant promise for redefining cardiovascular management and improving outcomes in HF.

Background: Acute myocardial infarction (AMI) is a major global health burden, with current diagnostic biomarkers often limited by delayed elevation and low specificity. Exosomes have emerged as promising non-invasive biomarkers for cardiovascular diseases.

Methods: Transcriptomic datasets from the Gene Expression Omnibus were integrated with candidate exosome-related gene sets to identify differentially expressed exosome-related genes (DEEGs) in AMI. Functional enrichment analyses were performed to explore biological functions. Machine learning algorithms including LASSO, Random Forest, and SVM-RFE were applied for feature selection. A diagnostic classification model was constructed and its discriminatory performance was evaluated. In silico drug prioritization was performed using the DSigDB database and molecular docking analysis. Plasma-derived exosomes from AMI patients and healthy controls were isolated for experimental validation, followed by quantitative real-time PCR analysis of candidate genes.

Results: A total of 273 differentially expressed genes were identified, including 27 DEEGs. Enrichment analysis revealed pathways related to neutrophil activation, NOD-like receptor signaling, and extracellular matrix organization. Six key genes, including S100A9, MMP9, FN1, NLRP3, CD55, and ITLN1 were selected as candidate diagnostic biomarkers. The multigene model demonstrated good diagnostic discrimination within the merged training cohort, while individual genes retained diagnostic value in an independent dataset. Several candidate compounds, including losartan, metoprolol, and pioglitazone, showed favorable binding affinities to key targets in molecular docking analyses. Transmission electron microscopy and nanoparticle tracking analysis confirmed the successful isolation of plasma exosomes, and qRT-PCR revealed significantly elevated expression of the six candidate genes in AMI-derived exosomes.

Conclusions: This integrative study identifies a set of exosome-associated genes with potential diagnostic relevance in AMI and provides exploratory in silico drug candidates targeting these biomarkers. These findings are hypothesis-generating and warrant further validation in large, prospectively collected cohorts and functional studies before clinical application.