Background: Heart failure (HF) is a chronic disease with high morbidity and mortality among older populations. Chronic HF ultimately affects both the right (RV) and left (LV) ventricles and often presents with extra-cardiac outcomes including pulmonary hypertension (PH). Study of biventricular failure and its extra-cardiac consequences has been challenging in pre-clinical models, suggesting new models may be beneficial to uncover new mechanisms of disease. Potassium channels are implicit regulators of vascular tone and are strongly but independently associated with PH and LV dysfunction.

Aim: We hypothesized that deletion of the potassium rectifier channel Kv1.5 would cause biventricular HF, thus representing a new model from which to understand ventricle-specific mechanisms of HF.

Methods and Results: We used a model of global vasoconstriction by genetic deletion of potassium rectifier channel Kv1.5 (Kv1.5 KO). Male and female mice were studied at middle age (12-13 months) as this is when HF risk begins to increase with age. In response to Kv1.5 KO, both the LV and RV experienced elevated afterload. While Kv1.5 KO mice developed RV systolic dysfunction with hypertrophy and fibrosis, the LV developed mild hypertrophy and diastolic dysfunction. Consistent with biventricular remodeling, Kv1.5 KO mice also displayed higher liver and lung weights and exercise intolerance.

Conclusion: Deletion of Kv1.5 causes systemic and pulmonary vasoconstriction with distinct outcomes in the LV and RV. This model of biventricular dysfunction may be useful for studying extra-cardiac consequences of HF and understanding ventricle-specific mechanisms of disease.

Selective autophagy, as a crucial form of cellular autophagy, plays a vital role in the degradation of specific substances or organelles in cells. Different from traditional autophagy mechanisms, it precisely identifies and removes damaged or superfluous cellular components, such as lipids, mitochondria, or endoplasmic reticulum, thereby maintaining cellular homeostasis. In recent years, research has revealed a close relationship between selective autophagy and cardiovascular diseases (CVDs). Dysfunction in selective autophagy may promote pathological damage or disease progression in various CVDs, including atherosclerosis, heart failure, ischemic heart disease, and metabolic cardiomyopathy. In this review, we focused on summarizing the mechanisms of specific selective autophagy pathways, including lipophagy, mitophagy, and reticulophagy in CVDs. Furthermore, we analyzed the potential applications and underlying mechanisms of small-molecule compounds, which could target selective autophagy for the treatment of CVDs. We aimed to provide a new theoretical foundation for the prevention and treatment of CVDs.

Cardiovascular disease (CVD) is the leading cause of global morbidity and mortality, with epigenetic mechanisms playing a pivotal role in its pathogenesis. This review synthesizes current evidence on sex-specific epigenetic regulation in cardiac health and disease, highlighting DNA methylation, histone modifications, and non-coding RNAs as key mediators. Epigenetic processes govern cardiac development, remodeling, and responses to injury, with sex chromosomes, sex hormones, and environmental factors contributing to dimorphic patterns. Developmental programming establishes early sex biases in chromatin architecture while aging and clonal hematopoiesis amplify these differences via mutations in epigenetic modulators. Therapeutic strategies targeting epigenetic regulators hold promise but require sex-tailored approaches to optimize efficacy and minimize off-target effects. This review underscores the critical need for sex-stratified research to advance precision medicine for CVD.