GJA5 and Myocardial fibrosis: Angiotensin II (Ang II) substantially downregulates atrial Cx40 expression (Western blot detects >50% reduction in Cx40 protein) by activating NF-κB and TGF-β1 pathways while upregulating collagen I and matrix metalloproteinases, directly promoting myocardial fibrosis [41].