Korean J Physiol Pharmacol.  2010 Oct;14(5):299-304. 10.4196/kjpp.2010.14.5.299.

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

Affiliations
  • 1Department of Pharmacology, Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717, Korea. hcchoi@med.yu.ac.kr

Abstract

Losartan is a selective angiotensin II (Ang II) type 1 (AT1) 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 G0/G1 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.

Keyword

AMP-activated protein kinase (AMPK); Angiotensin II type 1 (AT1) receptor antagonist; Losartan; Vascular smooth muscle cells (VSMCs); Proliferation

MeSH Terms

Acetyl-CoA Carboxylase
AMP-Activated Protein Kinases
Angiotensin II
Blotting, Western
Cell Cycle
Cell Cycle Checkpoints
Cell Proliferation
Contracts
Cyclin D
Cyclin E
Cyclins
Losartan
Muscle, Smooth, Vascular
Phosphorylation
Proteins
RNA, Small Interfering
AMP-Activated Protein Kinases
Acetyl-CoA Carboxylase
Angiotensin II
Cyclin D
Cyclin E
Cyclins
Losartan
Proteins
RNA, Small Interfering
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