Emerging Molecular Pathways in the Pathogenesis of Cardiovascular Diseases: A Comprehensive Review

Abstract

Cardiovascular diseases (CVDs) have been the leading killer since 1970. 18.71% of people died due to CVDs in the last decade which makes it imperative to go beyond traditional disease risk factor control strategies towards gaining the molecular pathogenesis. This review combines the most recent developments in molecular cardiology with numerous examples of the contribution of endothelial dysfunction, chronic inflammation, oxidative stress, and metabolic reprogramming in the pathogenesis of CVD progression. Major mechanisms include eNOS uncoupling, EndoMT, VSMC phenotypic switching and metabolites of gut microbiome, including TMAO, that drive atherosclerosis. The coming together of single-cell transcriptomics, multi-omics data and artificial intelligence is making it possible to resolve cellular heterogeneity and intercellular crosstalk like never before, leading towards the next step towards precision medicine. Novel therapeutic strategies are on the horizon including anti-inflammatory agents (e.g. Colchicine), redox-modulating therapy, epigenetic modulators, RNA based therapy (e.g siRNA for PCSK9) and microbiome-targeted therapy. These advancements have resulted in revolution in dimension from symptomatic treatment to mechanism-based specific therapy of reversing of underlying molecular defect in CVD.