The Yes-associated protein (YAP) pathway regulates cardiomyocyte proliferation, apoptosis, and immune homeostasis, with dual cardiac pathophysiological roles: aberrant activation worsens heart failure (HF), while targeted inhibition of YAP restores myocardial health. This study explores how aerobic exercise and Verteporfin intervention mediate YAP signaling to mitigate HF. The study uses a pressure overload-induced HF animal model to evaluate the effects of aerobic exercise, YAP inhibition, and their combination. Aerobic exercise preserved YAP abundance and suppressed phosphorylation-YAP overexpression in TAC-induced heart failure. This improves mitochondrial ultrastructure and cardiac function. YAP inhibition attenuates maladaptive remodeling by modulating macrophage polarization, downregulating M1 and upregulating M2 markers. The combination of aerobic exercise and YAP inhibition synergistically reduces fibrosis, hypertrophy, inflammation, and restores cardiac function. These findings identify YAP as a key target for exercise-mediated cardioprotection, and the potential mechanism may be through protecting mitochondrial integrity and immune homeostasis. This study offers novel insights into exercise-regulated YAP signaling as a therapeutic strategy for pressure overload-induced HF.
PRKAG2 cardiac syndrome (PCS) is a metabolic storage cardiomyopathy caused by pathogenic variants in the PRKAG2 gene encoding the γ2-subunit of AMP-activated protein kinase (AMPK). It is defined by left ventricular hypertrophy, ventricular preexcitation and progressive conduction system disease accompanied by early-onset atrial arrhythmias. This review systematically evaluates PCS, outlining its clinical manifestations, genotype-phenotype spectrum, and diagnostic clues that distinguish it from sarcomeric hypertrophy. It explores underlying pathophysiological mechanisms, detailing how chronic AMPK activation drives glycogen accumulation via allosteric G6P activation of glycogen synthase, following a biphasic temporal model from early GLUT4-mediated glucose flooding to late metabolic feedback suppression. It further examines how Akt–mTOR hyperactivation fosters hypertrophy and how activated fasciculoventricular pathways mediate preexcitation. Finally, it reviews current supportive clinical management and highlights emerging precision medicine frontiers—including RNA-based silencing, pharmacological pathway inhibitors, and CRISPR-Cas9 gene editing—that aim to shift PCS care toward targeted disease modification.
This cross-sectional exploratory study investigates the potential of metabolomics to differentiate between stable coronary artery disease (CAD) and acute myocardial infarction (AMI) through Nuclear Magnetic Resonance (NMR) spectroscopic analysis. The study identifies distinct metabolic profiles for each condition, revealing significant variations in metabolite levels, particularly lactic acid, which is a key metabolic product of anaerobic glycolysis, emerges as a prominent marker in AMI patients, reflecting acute ischemic stress and providing insight into adverse outcomes associated with high lactate levels. Another metabolite found in the present study was hypoxanthine, which is key biomarker for myocardial ischemia. These findings underscore the potential of metabolomics in combination with pathway analysis in distinguishing between CAD and AMI and highlight the metabolic dysregulation that occurs in these diseases. Our results suggest that these metabolites could serve as potential biomarkers, paving the way for personalized prognostic and diagnostic strategies. Further large-scale studies are necessary to validate these findings and incorporate them into clinical practice.
Acute ischemic stroke can trigger cardiac injury independent of primary coronary disease, producing manifestations ranging from troponin elevation and electrocardiographic abnormalities to arrhythmias, left ventricular dysfunction, Takotsubo syndrome, and sudden cardiac death, collectively termed stroke-heart syndrome. Cardiac complications affect roughly a quarter of patients within the first month, cluster in the first days, and are the second most frequent cause of death after stroke; older patients, those with severe or insular strokes, those with cardiometabolic comorbidity, and women are disproportionately affected. We propose the Neurocardiac Injury Cascade, an eight-stage framework comprising brain lesion, central autonomic network disruption, catecholamine storm, immune activation, coronary microvascular dysfunction, myocardial injury, electrical instability, and cardiac remodeling. Stages three to five are explicitly modeled as a concurrent, mutually reinforcing module rather than as sequential steps, and each stage is given a definition, an expected time window, and a measurable signature. By organizing these events sequentially, the model links mechanisms with biomarker evolution, imaging findings, and stage-specific therapeutic opportunities. We further propose that chronic comorbidity, principally hypertension and diabetes, does not add stages but sets the gain at existing ones, which has direct consequences for the design of preclinical models and clinical trials. We highlight the role of the insular cortex and lateralized autonomic output, position Takotsubo syndrome as the severe phenotype of the cascade, and address the heterogeneity of post-stroke troponin elevation. This framework integrates diagnosis, risk stratification, and mechanism-based therapies to advance precision neurocardiology and guide future translational and clinical research.
Circulating cell-free DNA (cfDNA) has emerged as a potential biomarker for cardiovascular injury, yet its clinical relevance in acute myocardial infarction (AMI) remains underexplored. cfDNA from 107 AMI patients and 32 healthy controls were isolated and its associations with clinical, demographic and biochemical profiling were explored. Patients were stratified by chest pain duration (0–24 h) to assess cross-sectional temporal trends. cfDNA levels showed six-fold elevation in AMI patients compared to controls and were associated with adverse cardiometabolic and lifestyle risk factors. cfDNA levels increased progressively with chest pain duration, peaking for 18–24 h (median:55.31 ng/mL), and strongly correlated with hs-cTnT (rho = 0.535) and NT-proBNP (rho = 0.615) during this phase. Overall diagnostic performance of cfDNA was good (AUC = 0.858), which further improved in late-phase AMI (AUC = 0.904). Strong diagnostic performance of cfDNA, particularly in the late phase AMI, suggests its potential as a complementary tool to existing cardiac biomarkers.
