MPS 13-09 AT2 RECEPTOR STIMULATION INHIBITS PHOSPHATE-INDUCED VASCULAR CALCIFICATION. (September 2016)

• Record Type: Journal Article
• Authors: Kukida, Masayoshi; Mogi, Masaki; Iwanami, Jun; Nakaoka, Hirotomo; Min, Li-Juan; Higaki, Akinori; Okura, Takafumi; Higaki, Jitsuo; Horiuchi, Masatsugu
• Is Part Of: Journal of hypertension. Volume 34:(2016) Supplement 1
• Publication Date: 2016-09
• Subjects: Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/01.hjh.0000501055.97675.58
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Objective: A variety of evidence suggests that angiotensin II type 2 (AT2 ) receptor stimulation exerts beneficial counter-regulatory roles against angiotensin II type 1 (AT1 ) receptor action in cardiovascular remodeling. Whereas, vascular calcification is a common finding in atherosclerosis and a serious problem in diabetic and chronic kidney disease. Moreover, some recent reports suggest that the renin-angiotensin system plays a role in the pathogenesis of cardiovascular remodeling. Here, we examined the possibility of whether AT2 receptor stimulation is involved in the inhibitory effects on phosphate-induced vascular calcification. Design and Method: Ex vivo study, thoracic aorta sections were prepared from C57BL/6 (WT), AT2 receptor-knockout (AT2 KO) and smooth muscle cell-specific AT2 receptor overexpressed (smAT2 Tg) mice and then cultured in DMEM supplemented with inorganic phosphate (Pi) to induce vascular calcification. Morphometric assessment of medial calcium deposition was quantitatively performed, and the amount of dissolved calcium was measured. In vitro study, primary vascular smooth muscle cells were prepared from WT, AT2 KO, smAT2 Tg mice and cultured like ex vivo study. Results: Ex vivo, Vascular calcification in thoracic aortas of smAT2 Tg mice was significantly attenuated compared with AT2 KO and WT mice. In vitro, VSMC cultured in DMEM containing high-phosphate showed dose- and time-dependent increase in mineral deposition. Vascular calcification induced by phosphate-stimulation markedly attenuated in smAT2 Tg mice compared with other mice. Conclusions: Our results suggest that AT2 receptor stimulation is an efficient endogenous vasoprotective factor in vascular calcification. The selective stimulation of AT2 receptor may decrease the risk of vascular calcification and subsequent adverse cardiovascular events during chronic kidney disease.