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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2016.1
- 수록면
- 523 - 528 (6page)
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Urotensin II (UII) is a potent vasoactive peptide and mitogenic agent to induce proliferation of various cells including vascular smooth muscle cells (VSMCs). In this study, we examined the effects of a novel UII receptor (UT) antagonist, KR-36676, on vasoconstriction of aorta and proliferation of aortic SMCs. In rat aorta, UII-induced vasoconstriction was significantly inhibited by KR-36676 in a concentration-dependent manner. In primary human aortic SMCs (hAoSMCs), UII-induced cell proliferation was significantly inhibited by KR-36676 in a concentration-dependent manner. In addition, KR-36676 decreased UII-induced phosphorylation of ERK, and UII-induced cell proliferation was also significantly inhibited by a known ERK inhibitor U0126. In mouse carotid ligation model, intimal thickening of carotid artery was dramatically suppressed by oral treatment with KR-36676 (30 mg/kg/day) for 4 weeks compared to vehicle-treated group. From these results, it is indicated that KR-36676 suppress UII-induced proliferation of VSMCs at least partially through inhibition of ERK activation, and that it also attenuates UII-induced vasoconstriction and vascular neointima formation. Our study suggest that KR-36676 may be an attractive candidate for the pharmacological management of vascular dysfunction.
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참고문헌 (35)
참고문헌 신청
Ames, N. P. / 1999 / Effect of Environment and Genotype on Durum Wheat Gluten Strength and Pasta Viscoelasticity / Cereal Chem 76:582~586
Ames, R. S. / 1999 / Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14 / Nature 401:282~286
Bottrill, F. E. / 2000 / Human urotensin-II is an endothelium-dependent vasodilator in rat small arteries / Br. J. Pharmacol 130:1865~1870
Choi, E. T. / 2004 / Beta3-integrin mediates smooth muscle cell accumulation in neointima after carotid ligation in mice / Circulation 109:1564~1569
Coulouarn, Y. / 1998 / Cloning of the cDNA encoding the urotensin II precursor in frog and human reveals intense expression of the urotensin II gene in motoneurons of the spinal cord / Proc. Natl. Acad. Sci. U.S.A 95:15803~15808
Ames, R. S. / 1999 / Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14 / Nature 401:282~286
Bottrill, F. E. / 2000 / Human urotensin-II is an endothelium-dependent vasodilator in rat small arteries / Br. J. Pharmacol 130:1865~1870
Choi, E. T. / 2004 / Beta3-integrin mediates smooth muscle cell accumulation in neointima after carotid ligation in mice / Circulation 109:1564~1569
Coulouarn, Y. / 1998 / Cloning of the cDNA encoding the urotensin II precursor in frog and human reveals intense expression of the urotensin II gene in motoneurons of the spinal cord / Proc. Natl. Acad. Sci. U.S.A 95:15803~15808
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