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bioRxiv · 10.1101/2025.05.31.657024

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

Shinde, P. L.·Kumar, V.·Singh, S.·Sivakumar, K. C.·Mishra, R.
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Abstract

Biological aging (BA) and pressure overload-induced cardiac hypertrophy (PO-CH) are marked by myocardial thickening, fibrosis, and functional decline, culminating in an increased risk of heart failure. Effective clinical management requires biomarkers that not only track disease progression but also monitor therapeutic response. Using Amalaki Rasayana (AR), a cardioprotective nutraceutical-based medicine, in rat models of BA and PO-CH, we identified a panel of serum biomarkers whose treatment-induced decline was associated with disease regression. Among them, galectin-3 emerged in both full-length and oligomeric C-epitope cleaved forms, with the latter closely linked to pathological surface remodeling. Treatment with AR and its bioactive component gallic acid (GA) suppressed extracellular galectin-3 C-epitope oligomer accumulation by inhibiting full-length galectin-3 secretion through phosphorylation-dependent mechanisms and promotion of intracellular retention. Concurrently, serum levels of atrial natriuretic peptide (ANP), cyclophilin A (PPIA), and albumin (ALB) were consistently modulated by therapy. Validation in sera from elderly individuals and cardiac hypertrophy patients responding to conventional treatments supported the translational relevance of this biomarker panel. These findings establish a novel, mechanistically grounded biomarker set--galectin-3 C-epitope, ANP, PPIA, and ALB--for monitoring therapeutic response in cardiac hypertrophy, and position AR as a promising medicinal intervention against age- and pressure-induced cardiac pathology. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=87 SRC="FIGDIR/small/657024v3_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@2498d8org.highwire.dtl.DTLVardef@aeb4fcorg.highwire.dtl.DTLVardef@1ec2f9eorg.highwire.dtl.DTLVardef@12a4392_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LIGalectin-3 C-epitope, ANP, PPIA, and ALB are elevated in aging and pressure overload driven left ventricular hypertrophy. C_LIO_LIAmalaki rasayana (AR) and Gallic Acid (GA) reduce these markers in cardiac tissue and circulation. C_LIO_LIAR and GA inhibit galectin-3 secretion and oligomeric binding to cardiomyocyte surfaces. C_LIO_LIAR and GA regulation predominantly occurs via phosphorylation-dependent cytoplasmic retention of galectin-3. C_LIO_LIThese markers serve as potential therapeutic targets and diagnostic biomarkers. C_LI

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Shinde, P. L., Kumar, V., Singh, S., Sivakumar, K. C., Mishra, R.. 2025-06-03. 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. https://doi.org/10.1101/2025.05.31.657024

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