Losartan Inhibits Vascular Smooth Muscle Cell Proliferation through Activation of AMP-Activated Protein Kinase

Title
Losartan Inhibits Vascular Smooth Muscle Cell Proliferation through Activation of AMP-Activated Protein Kinase
Author(s)
최형철김정은
Keywords
SPONTANEOUSLY HYPERTENSIVE-RATS; AT(1) RECEPTOR ANTAGONIST; FATTY-ACID OXIDATION; ANGIOTENSIN-II; INSULIN-RESISTANCE; GLUCOSE-UPTAKE; IN-VIVO; ATHEROSCLEROSIS; IDENTIFICATION; TELMISARTAN
Issue Date
201010
Publisher
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
Citation
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY, v.14, no.5, pp.299 - 304
Abstract
Losartan is a selective angiotensin II (Ang II) type 1 (AT(1)) receptor antagonist which inhibits vascular smooth muscle cells (VSMCs) contraction and proliferation We hypothesized that losartan may prevent cell proliferation by activating AMP-activated protein kinase (AMPK) in VSMCs VSMCs were treated with various concentrations of losartan AMPK activation was measured by Western blot analysis and cell proliferation was measured by MTT assay and flowcytometry Losartan dose- and time-dependently increased the phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC) in VSMCs Losartan also significantly decreased the Ang II- or 15% FBS-induced VSMC proliferation by inhibiting the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E Compound C, a specific inhibitor of AMPK, or AMPK siRNA blocked the losartan-induced inhibition of cell proliferation and the G(0)/G(1) cell cycle arrest These data suggest that losartan-induced AMPK activation might attenuate Ang II-induced VSMC proliferation through the inhibition of cell cycle progression
URI
http://hdl.handle.net/YU.REPOSITORY/23531http://dx.doi.org/10.4196/kjpp.2010.14.5.299
ISSN
1226-4512
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의과대학 > 약리학교실 > Articles
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