1. Cyclic Strain and Hypertension Increase Osteopontin Expression in the Aorta.
- Author
-
Caesar C, Lyle AN, Joseph G, Weiss D, Alameddine FMF, Lassègue B, Griendling KK, and Taylor WR
- Abstract
Hypertension has a direct impact on vascular hypertrophy and is a known risk factor for the development of atherosclerosis. Osteopontin (OPN) has emerged as an important protein mediator of inflammation and remodeling of large arteries. However, its role and mechanism of regulation in the setting of hypertension is still unknown. Our objectives for this study were therefore to investigate the role of OPN in hypertension-induced vascular remodeling and inflammation. OPN Knockout (KO) and wild type (WT) mice were made hypertensive with angiotensin II (Ang II) infusion for seven days. We observed that OPN KO aortas were protected against Ang II-induced medial hypertrophy and inflammation, despite comparable increases in systolic blood pressure (SBP) in both groups. OPN expression was increased in WT aortas from hypertensive mice (induced by either Ang II or norepinephrine). OPN expression was increased in aortic smooth muscle cells (SMCs) subjected to cyclic mechanical strain suggesting that mechanical deformation of the aortic wall is responsible in part for the increased OPN expression induced by hypertension. Finally, we utilized hypertensive transgenic smooth muscle cell-specific catalase overexpressing (Tg
SMC-Cat ) mice to determine the role of H2 O2 in mediating hypertension-induced increases in OPN expression. We also found that the hypertension-induced increase in OPN expression was inhibited in transgenic smooth muscle cell-specific catalase overexpressing (TgSMC-Cat ) mice, suggesting that H2 O2 , plays a vital role in mediating the hypertension-induced increase in OPN expression. Taken together, these results define a potentially important role for OPN in the pathophysiology of hypertension., Competing Interests: CONFLICT OF INTEREST Christa Caesar, Alicia N. Lyle, Giji Joseph, Daiana Weiss, Fadi M. F. Alameddine, Bernard Lassègue, Kathy K. Griendling, and W. Robert Taylor have no conflicts of interest to disclose.- Published
- 2017
- Full Text
- View/download PDF