Cardiogenetics

The 2025 Editor’s Choice papers [...]

Background: Hypertrophic cardiomyopathy (HCM) exhibits clinical heterogeneity and age-related penetrance, yet its molecular basis across adulthood remains incompletely understood. This study aimed to characterize age-dependent transcriptomic signatures and identify conserved molecular features across adult HCM. Methods: Left ventricular RNA sequencing data from the GSE141910 dataset were analyzed by comparing three age-stratified HCM groups (18–39, 40–59, and ≥60 years) with corresponding age-matched controls. Differentially expressed genes (DEGs) were identified using GEO2R, followed by functional enrichment and protein–protein interaction (PPI) network analysis. Results: A total of 498 DEGs were shared across all age tertiles, while 439, 594, and 353 DEGs were specific to the youngest, middle-aged, and oldest groups, respectively. Shared DEGs exhibited an extracellular matrix (ECM)-related functional profile and formed PPI modules associated with ECM homeostasis and immune regulation. Age-specific analyses revealed enrichment of adaptive immune pathways in younger patients, cell cycle- and interferon-associated processes in the middle-aged group, and ECM remodeling together with senescence-associated processes in older patients. Hub gene analysis further highlighted distinct age-dependent molecular signatures. Conclusions: Our findings suggest that adult HCM is characterized by a conserved fibrotic core accompanied by age-dependent biological programs, providing a framework for future studies investigating age-informed biomarkers and therapeutic targets.

Background: Ischemic stroke (IS) is a major cause of global disability, with outcomes increasingly dictated by post-ischemic neuroinflammation. Despite advances in reperfusion, many patients experience neurological decline due to divergent inflammatory responses. Objectives: This review synthesizes current evidence on inflammatory signaling, stroke genetics, and genetically informed precision medicine relevant to the interplay between interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and ischemic stroke outcomes. Methods: We reviewed evidence from genome-wide association studies, Mendelian randomization analyses, experimental studies, observational biomarker cohorts, and relevant cardiovascular anti-inflammatory trials. Evidence from non-stroke populations is identified as indirect and is not interpreted as proof of efficacy in ischemic stroke. Results: IL-6 and TNF-α signaling involves receptor- and context-dependent mechanisms that may have both harmful and protective effects after cerebral ischemia. Multi-omic studies of the chromosome 9p21 locus and ANRIL suggest potential links among vascular-cell regulation, inflammation, and atherosclerotic risk, although stroke-specific mechanistic evidence remains limited. Elevated inflammatory-marker concentrations have been associated with greater stroke severity and unfavorable outcomes; however, their independent prognostic value and optimal sampling strategy require further validation. Selective anti-inflammatory approaches provide biologically plausible strategies for future study, but genotype-guided anti-cytokine treatment is not established for acute ischemic stroke or post-stroke recovery. Conclusions: Stroke genetics and multi-omic approaches may contribute to future precision-medicine strategies, but their clinical utility requires validation in prospective, stroke-specific studies. Current evidence does not support routine cytokine genotyping or genotype-guided anti-cytokine treatment in ischemic stroke.