Altered phosphodiesterase 3-mediated cAMP hydrolysis contributes to a hypermotile phenotype in obese JCR:LA-cp rat aortic vascular smooth muscle cells: implications for diabetes-associated cardiovascular disease

Diabetes
Stuart J NethertonDonald H Maurice

Abstract

Cardiovascular diseases represent a significant cause of morbidity and mortality in diabetes. Of the many animal models used in the study of non-insulin-dependent (type 2) diabetes, the JCR:LA-cp rat is unique in that it develops insulin resistance in the presence of obesity and manifests both peripheral and coronary vasculopathies. In this animal model, arterial vascular smooth muscle cells (VSMCs) from homozygous obese (cp/cp) rats, but not from age-matched healthy (+/+ or + /cp, collectively defined +/?) littermates, display an " activated" phenotype in vitro and in vivo and have an elevated level of cAMP phosphodiesterase (PDE) activity. In this report, we confirm that cp/cp rat aortic VSMCs have an elevated level of PDE3 activity and show that only particulate PDE3 (PDE3B) activity is elevated. In marked contrast to results obtained in + /? VSMCs, simultaneous activation of adenylyl cyclase and inhibition of PDE3 activity in cp/cp VSMCs synergistically increased cAMP. Although PDE3 inhibition did not potentiate the antimigratory effects of forskolin on +/? VSMCs, PDE3 inhibition did markedly potentiate the forskolin-induced inhibition of migration of cp/cp-derived VSMCs. Although PDE3 activity was elevated in cp/cp rat aor...Continue Reading

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Citations

Jul 9, 2009·JAMA : the Journal of the American Medical Association·Ramachandran S VasanStefan Blankenberg
Nov 1, 2005·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Xiangzhi Zhou, Per-Olof Westlund
Dec 25, 2003·Journal of Smooth Muscle Research = Nihon Heikatsukin Gakkai Kikanshi·Takayuki MatsumotoKatsuo Kamata
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May 12, 2005·American Journal of Physiology. Endocrinology and Metabolism·Hisham S Elbatarny, Donald H Maurice
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May 17, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Takayuki MatsumotoKatsuo Kamata
May 8, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Takayuki MatsumotoKatsuo Kamata
Jun 10, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Takayuki MatsumotoKatsuo Kamata
Jan 5, 2006·Canadian Journal of Physiology and Pharmacology·Timothy J Bloom
Apr 4, 2020·Current Pharmaceutical Design·Javier Blanco-Rivero, Fabiano E Xavier

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