These findings indicate that EC Smad 2 is a critical mechano-transducer from the association of integrins and TGF-β receptors, whose activation is differentially regulated by different ECM proteins, i.e., FN and LM, and may consequently contribute to the formation and progression of atherosclerosis in the disturbed flow region of arterial trees. The gene discussed is FN1; the disease is atherosclerosis.