Excessive activation or abnormal signaling of TGF-β1 prompts VSMCs to transition to a synthetic phenotype, reducing their contractile ability and promoting ECM overproduction via classical and non-classical TGF-β pathways, including TGF-β/smad, MAPK (ERK1/2, p38 MAPK, JNK), NF-κB, and PI3K/Akt, which collectively contribute to vascular stiffness, dysfunction, decreased compliance, and the development of cardiovascular diseases such as hypertension, atherosclerosis, and aneurysms [50,132,133,134,135,136]. This evidence concerns the gene TGFB1 and atherosclerosis.