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(Circulation Research. 2006;99:238.)
© 2006 American Heart Association, Inc.

Editorials

Rho-Kinase

A Potential Link Between Hypercholesterolemia and Abnormal Vascular Smooth Muscle Contraction

James K. Liao

From the Vascular Medicine Research Unit, Cardiovascular Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass.

Correspondence to James K. Liao, MD, Brigham and Women’s Hospital, 65 Landsdowne St, Rm 275, Cambridge, MA 02139. E-mail jliao@rics.bwh.harvard.edu

See related article, pages 299–306

Key Words: cholesterol • Rho kinase • calcium • smooth muscle • contraction

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Although elevated serum cholesterol levels and hypertension are independent risk factors for cardiovascular disease, far too often they are manifested in the same individual.¹ Whether this is a coincidental finding between 2 highly prevalent risk factors or perhaps because of some mechanistic link between these 2 processes is unclear. Regardless, the concomitant treatment of hypercholesterolemia and hypertension has yielded additive and possibly synergistic reductions in cardiovascular events.²

Previous studies attempting to link hypercholesterolemia with abnormal vascular smooth muscle (SMC) contractions have focused on the endothelium. Hypercholesterolemia and atherosclerosis impair the production and/or availability of endothelium-derived NO, leading to endothelial dysfunction and abnormal vascular reactivity.^3–5 Indeed, acute lowering of serum cholesterol with low-density lipoprotein-apheresis or with statin therapy improves endothelium-dependent relaxations.^6–8 These findings suggest that the endothelium serves as the primary mediator of the inhibitory effect of hypercholesterolemia on vascular motor function. The direct effect of cholesterol on SMC, however, is less well understood as endothelium-independent vasorelaxations to nitroprusside are often unaltered in hypercholesterolemia or in patients with atherosclerosis.^6,8,9

In the present study, Morikage et al extend the effects of cholesterol on vascular reactivity to changes in SMC contractions.¹⁰ They showed that elevated serum cholesterol levels were associated with increased calcium sensitization of SMC through the sphingosylphosphorylcholine (SPC)/Rho-kinase (ROCK)-mediated pathway in humans and rabbits. This enhanced SMC contraction was observed only with ROCK activator SPC and not with phenylephrine or potassium; was accompanied by minimal changes in intracellular calcium concentration; and was unaffected by addition of the eNOS inhibitor, N^G-monomethyl-. . . [Full Text of this Article]

Related Article:

Cholesterol Primes Vascular Smooth Muscle to Induce Ca² Sensitization Mediated by a Sphingosylphosphorylcholine–Rho-Kinase Pathway: Possible Role for Membrane Raft

Noriyasu Morikage, Hiroko Kishi, Masafumi Sato, Fengling Guo, Satoshi Shirao, Takashi Yano, Masaaki Soma, Kimikazu Hamano, Kensuke Esato, and Sei Kobayashi
Circ. Res. 2006 99: 299-306. [Abstract] [Full Text] [PDF]

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