Proteomic Profiling of Fucoidan’s Cardioprotective Effects in a Pressure Overload Model

Cardiac hypertrophy and fibrosis are hallmark responses to pressure overload, driving the progression of heart failure. Fucoidan, a sulfated polysaccharide derived from brown algae, has demonstrated anti-inflammatory and antioxidant effects in cardiovascular models. Building on prior evidence of its ability to suppress galectin-3 secretion and re-duce myocardial fibrosis, this study investigates the proteomic mechanisms underlying fucoidan’s cardioprotective actions in a murine model of transverse aortic constriction (TAC). Male mice subjected to TAC received either fucoidan or vehicle control. Cardiac function was evaluated via transthoracic echocardiography, and histological analyses quantified hypertrophy and fibrosis. Left ventricular tissues, enriched for fibroblasts and cardiomyocytes, underwent proteomic profiling using liquid chromatography–tandem mass spectrometry. Differentially expressed proteins were identified using stringent cri-teria (log₂ fold change < 0.58; P < 0.001). Fucoidan treatment significantly attenuated cardiac remodeling, with proteomic signatures revealing consistent upregulation of mi-tochondrial enzymes, ribosomal subunits, and cytoskeletal proteins in fucoidan-treated TAC mice compared to untreated controls. Enrichment analysis indicated activation of pathways related to energy metabolism, mitochondrial biogenesis, protein synthesis, and structural integrity. Notably, proteins involved in oxidative stress regulation, iron-sulfur cluster assembly, and extracellular matrix remodeling were restored toward baseline levels. These findings suggest that fucoidan mitigates pressure overload-induced cardiac remodeling through coordinated modulation of mitochondrial function, translational machinery, and cytoskeletal architecture. The study provides proteomic evidence sup-porting fucoidan as a promising marine-derived therapeutic candidate for heart failure.