Prevention of aortic fibrosis by TV-acetyl-seryl-aspartyl-lysyl-proline II-induced hypertension

摘要

hypertension is associated with large conduit artery hypertrophy and an increase in extracellular matrix (ECM) content, especially collagen. Fibrosis is a major component of hypertensive vascular disease, causing vascular stiffness and arteriosclerosis (20, 37). Angiotensin II (ANG II) contributes to vascular injury by inducing inflammation, oxidative stress, excessive deposition of ECM, and hypertrophy and/or hyperplasia of vascular smooth muscle cells (VSMCs) (10). ANG H via its type 1 (ATi) receptor initiates activation of intracellular signaling cascades, including protein kinase C (PKC) activation. PKC-dependent activation of NAD(P)H oxidase leads to creased oxidative stress and inflammation, which play essen-tial roles in vascular disease (1, 10, 19, 36). ANG II also induces vascular fibrosis by stimulating transforming growth factor-beta1 (TGF-pl), which mediates its profibrotic effects by activating receptor-associated Smads (R-Smads, including Smad2 and Smad3) (35). Inhibitory Smads (I-Smads, i.e., Smad6 and Smad7) block TGF-beta signaling by binding to TGF-beta receptor type 1 receptors or by competing with activated R-Smad for binding to Smad4 (48).