These data build on our previous studies showing the following: 1) shear force can activate latent TGF-β1 released from platelets in vitro;18 2) plasma TGF-β1 levels increase over time in parallel with wall shear stress in the LA100 mouse model of AS;23 3) megakaryocyte and platelet-derived TGF-β1 accounts for ∼45% of plasma TGF-β1 as judged by mice with targeted deletion of platelet TGF-β1;22 and 4) thiol-disulfide exchange mediated by PDI contributes to activation of TGF-β1.18 Here, P4HB is linked to aortic stenosis.