Therapeutic Advancement in Cardiovascular Disorders: Molecular Mechanisms, Emerging Targets and Translational Perspectives

Abstract

Cardiovascular disorders (CVD) have been addressed as the leading cause of global mortality and morbidity which majorly includes atherosclerosis, hypertension, heart failure, arrhythmias and cardiomyopathies. Its pathogenesis involves various interconnected molecular mechanisms such as endothelial dysfunction, oxidative stress, chronic inflammation, mitochondrial impairment, lipid dysregulation, fibrosis and genetic alterations. The conventional pharmacological strategy of CVD includes statins, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), calcium channel blockers and antiplatelet agents. Clinically, though these medications have provided substantial improved outcomes but its long-term usage has been frequently associated with drug resistance, hepatotoxicity, myopathy, renal dysfunction, bleeding risk and residual cardiovascular events. Moreover, these primarily target symptomatic and hemodynamic abnormalities rather than the underlying molecular pathology. Recent advances in molecular cardiology and translational medicine have facilitated the development of targeted therapeutic strategies that primarily aims to overcome these limitations. Specifically, targeting dysregulated lipid pathophysiology, stains utilization has evolved to PCSK9 inhibitors and small interfering RNA (siRNA)-based therapeutics, such as inclisiran. Precision medication strategy has made the use of RNA therapeutics and CRISPR-Cas9-mediated which enable precise regulation of disease-associated genes. Regenerative stem cell therapies, on the other hand promoted myocardial repair and angiogenesis, while nanotechnology-based drug delivery systems improved therapeutic specificity and bioavailability. In parallel to this, AI-assisted precision cardiology has enabled early diagnosis, risk stratification, and individualized treatment planning strategies. However, despite these advances, challenges related to safety, delivery efficacy, ethical concerns and expense remain the major barriers to widespread clinical translation of these therapeutic advancements in cardiac patients. Keywords: Cardiovascular disorders, Conventional cardiac-therapeutics, PCSK9 inhibitors