Biologics for cardiovascular diseases: from bench to bedside

The rise of biologics, including recombinant proteins, gene therapies, and cell therapies, is reshaping the landscape of modern therapeutics, offering new strategies to address previously "undruggable" targets. Cardiovascular diseases (CVDs), the leading cause of mortality worldwide, remain inadequately managed by traditional therapies, but biologics offer a paradigm shift from symptom control to disease modification. This review provides a comprehensive analysis of biologics in cardiovascular medicine, focusing on five key biological processes: cardiac regeneration, cardiac reverse remodeling, genetic cardiomyopathy correction, vascular function modulation, and lipid metabolism modulation. Advances in cardiac regeneration are highlighted by the transplantation of pluripotent stem cells, direct reprogramming, stimulation of endogenous adult cardiomyocyte proliferation, and noncell strategies, all of which aim to restore cardiac tissue integrity. In reverse cardiac remodeling, therapies targeting key signaling pathways, metabolic processes, and contractility-enhancing agents offer promising new approaches for CVD management. The development of gene therapies targeting genetic cardiomyopathies, including gene replacement, genome editing, and gene silencing, is discussed. For vascular function modulation, therapies targeting angiotensinogen, natriuretic peptide receptor 1, and the gut microbiome have been explored as innovative approaches to regulate vascular tone and hemodynamics. Finally, lipid modulation therapies, including agents targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) and atherogenic lipoproteins, have redefined the management of dyslipidemia and cardiovascular risk. Collectively, these advancements underscore the transformative potential of biologics to provide targeted, personalized, and disease-modifying treatments for CVD. By addressing both the pathophysiological roots and clinical manifestations of CVDs, biologics represent a promising frontier in cardiovascular medicine.