JAK/STAT3/MMP9 Pathway Inhibition by Epigallocatechin-3-Gallate Alleviates Experimental Abdominal Aortic Aneurysm

Background: Epigallocatechin-3-gallate (EGCG) exhibits protective effects against abdominal aortic aneurysm (AAA), although its specific molecular mechanism remains unclear. Aberrant activation of the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway mediates matrix metallopeptidase 9 (MMP9) expression and cell apoptosis, which are critical to aortic wall damage and AAA progression. This study investigated whether EGCG mitigates AAA by targeting the JAK/STAT3/MMP9 axis.Methods: Rat in vivo AAA models were established via elastase infusion and CaCl2 exposure, with EGCG administered by daily oral gavage from 7 days before modeling to 28 days after modeling. Angiotensin II (Ang II)-treated rat aortic smooth muscle cells (RASMCs) were used for in vitro assays, combined with pretreatment with gradient concentrations of EGCG and rescue experiments using the JAK/STAT3 pathway activator RO8191. Morphological, histological and molecular analyses were systematically conducted to assess aortic pathological changes, RASMC viability, pathway activation and the expression of apoptosis- and extracellular matrix-related molecules.Results: EGCG significantly attenuated in vivo AAA progression, as shown by reduced aortic dilatation, attenuated aortic wall injury, restored elastic fiber integrity and Collagen I deposition, as well as suppressed JAK/STAT3 phosphorylation, cell apoptosis and MMP9 upregulation in aortic tissues (p < 0.05). In vitro, EGCG exerted no obvious cytotoxicity on RASMCs but concentration-dependently suppressed Ang II-induced JAK/STAT3 activation, cell apoptosis and MMP9 expression at both the protein and mRNA levels (p < 0.05). These protective effects were effectively reversed by RO8191 (p < 0.05).Conclusion: Collectively, EGCG alleviates experimental AAA progression through inhibition of the JAK/STAT3 signaling pathway and associated downregulation of MMP9 expression, providing a novel molecular basis for EGCG as a potential preventive strategy for AAA and supporting its promising clinical potential in AAA prevention.