Biologics Offer Paradigm Shift for Cardiovascular Diseases, Targeting Regeneration, Remodeling, and Lipid Metabolism

Despite advances, Cardiovascular Diseases (CVDs) remain the leading cause of mortality globally, with traditional therapies often falling short of achieving comprehensive disease modification. Current treatments primarily manage symptoms, leaving a significant unmet need for interventions that address the underlying pathophysiological roots. Biologics, encompassing recombinant proteins, gene therapies, and cell therapies, represent a crucial paradigm shift, offering the potential to target previously 'undruggable' pathways and fundamentally alter disease progression, moving beyond mere symptomatic relief.

This comprehensive review provides an in-depth analysis of the role of biologics in cardiovascular medicine, systematically categorizing advancements across five critical biological processes. The authors synthesized current research on strategies for cardiac regeneration, cardiac reverse remodeling, genetic cardiomyopathy correction, vascular function modulation, and lipid metabolism modulation. The review explores various therapeutic modalities within these areas, including stem cell transplantation, gene editing, and targeted protein therapies, to highlight their potential in addressing the complex pathophysiology of CVDs.

The review highlights significant progress in several areas of biologic development for CVD. In cardiac regeneration, strategies such as pluripotent stem cell transplantation, direct cellular reprogramming, and stimulation of endogenous adult cardiomyocyte proliferation are advancing towards restoring cardiac tissue integrity. For reverse cardiac remodeling, novel therapies targeting key signaling pathways, metabolic processes, and contractility-enhancing agents show promise in improving cardiac function. > The development of gene therapies, including gene replacement, genome editing, and gene silencing, is actively addressing genetic cardiomyopathies, offering the potential for definitive correction of inherited cardiac defects. Vascular function modulation is being explored through therapies targeting angiotensinogen, natriuretic peptide receptor 1, and even the gut microbiome to regulate vascular tone and hemodynamics. Furthermore, lipid modulation therapies, particularly agents targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) and atherogenic lipoproteins, have already redefined the management of dyslipidemia and significantly reduced cardiovascular risk.