Cyclic Strain and Hypertension Increase Osteopontin Expression in the Aorta

• Type of Material: Article
• Authors: Christa Caesar, Emory University; Alicia N. Lyle, Emory University; Giji Joseph, Emory University; Daiana Weiss, Emory University; Fadi M.F. Alameddine, Emory University; Bernard P Lassegue, Emory University; Kathy Griendling, Emory University; W Robert Taylor, Emory University
• Language: English
• Date: 2017-04-01
• Publisher: Springer Verlag (Germany)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016, Biomedical Engineering Society.
• Final Published Version (URL): http://dx.doi.org/10.1007/s12195-016-0475-2
• Title of Journal or Parent Work: Cellular and Molecular Bioengineering
• ISSN: 1865-5025
• Volume: 10
• Issue: 2
• Start Page: 144
• End Page: 152
• Grant/Funding Information: This work was supported by National Institutes of Health (NIH) PO1 HL095070 (WRT and KKG) and a pre-doctoral Grant from the American Heart Association (CC).
• Keywords: Norepinephrine; Life Sciences & Biomedicine; ACCELERATED ATHEROSCLEROSIS; CARDIOVASCULAR-DISEASE; DEFICIENT MICE; IN-VIVO; Cyclic strain; INFLAMMATION; Angiotensin II; SMOOTH-MUSCLE-CELLS; II-INDUCED HYPERTENSION; Smooth muscle cells; Cell & Tissue Engineering; ANGIOTENSIN-II; Cell Biology; OXIDATIVE STRESS; PRESSURE; Science & Technology; Vascular hypertrophy; Biophysics; Inflammation
• Research Categories: Biophysics, Medical; Health Sciences, Medicine and Surgery; Engineering, Biomedical

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 H 2 O 2 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 (Tg SMC-Cat ) mice, suggesting that H 2 O 2 , 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.