Galectin-3 C-epitope, ANP, PPIA, and albumin function as drug-responsive panel biomarkers and therapeutic targets in aging and pressure overload-induced cardiac hypertrophy

Abstract

Biological aging and pressure overload-induced left ventricular cardiac hypertrophy (PO-CH) is marked by myocardial thickening, fibrosis, and functional decline, heightening the risk of heart failure. To advance therapeutic monitoring and intervention, we aimed to identify drug-responsive biomarkers with functional relevance to disease progression. Using rat models of biological aging (BA) and PO-CH, we evaluated the cardioprotective effects of Amalaki Rasayana (AR), a traditional nutraceutical, and its bioactive constituent gallic acid (GA), while concurrently profiling candidate serum biomarkers. Galectin-3 was present in full-length and oligomeric forms, with C-terminal (C-epitope) homo-oligomers closely associated with pathological remodeling. AR and GA significantly reduced these oligomers via cytoplasmic retention and phosphorylation-dependent downregulation of galectin-3 secretion, mitigating maladaptive cardiomyocyte signaling. Levels of atrial natriuretic peptide (ANP), cyclophilin A (PPIA), and albumin (ALB) showed consistent changes, reinforcing their utility as therapeutic response indicators. Findings were validated in sera from aged humans and patients responsive to clinical treatment, confirming translational potential. This study establishes a novel biomarker panel-galectin-3 C-epitope, ANP, PPIA, and ALB-for monitoring treatment efficacy and positions AR as a promising intervention in cardiac hypertrophy.