Here, we demonstrate that ADAMTS1 (A Disintegrin and Metalloproteinase with Thrombospondin Motifs 1), significantly upregulated in endothelial cells (ECs) following MI, plays a pivotal role in regulating cardiac fibroblast activation through a novel mechanotransduction pathway involving integrin α8 (ITGα8). Here, ITGA8 is linked to myocardial infarction.