Atherosclerosis is a chronic inflammatory disease, and also characterized by both the innate and the adaptive immune responses. Lipid (cholesterol) retention is a classic hypothesis of atherogenesis. In human body, the cholesterol homeostasis is finely tuned by the balance between lipid uptake and efflux by macrophages. The rapid and unregulated uptake of oxidized LDL (oxLDL) by scavenger receptors (such as scavenger receptor-A (SR-A), CD36, and lectinlike oxLDL receptor-1 (LOX-1)) contributes to monocyte-derived foam cells in atherosclerotic lesions. Macrophages are also able to transport excessive cholesterol in peripheral tissues by cholesterol efflux or reverse cholesterol transport (RCT) pathways. This process is mediated by multiple cholesterol exporters such as the ATP-binding cassette transporters A1 (ABCA1), ABCG1, ABCG4, and SR- BI. Targeting lipid uptake and/or cholesterol efflux represents an effective therapeutic strategy to influence the development and progression of atherosclerotic lesions. The Rho-Associated Coiled-Coil Containing Protein Kinase (ROCK) isoforms, ROCK1 and ROCK2, are protein serine/threonine kinases of 160 kDa, and are downstream effectors of the small GTPase Rho. ROCK1 mRNA was ubiquitously expressed except in the brain and muscle, whereas ROCK2 mRNA was expressed abundantly in the brain, muscle, heart, lung and placenta. Indeed, ROCK is up-regulated by inflammatory stimuli, such as angiotensin II and interleukin-1β, lipopolysaccharide (LPS) and oxLDL. More recently, there are several excellent reviews  addressing the role of Rho/ROCK pathway in mediating multiple cellular functions and the use of ROCK inhibitors in cardiovascular diseases. ROCK has been shown to be up-regulated in inflammatory atherosclerotic lesions and administration of a RhoA/ROCK inhibitor (Y-27632, 30 mg/kg/d, 9 weeks) significantly decreased early atherosclerotic lesion formation. However, the roles of ROCK in more advanced stages of atherosclerosis (i.e., plaque rupture) as well as ROCK isoforms in the progression of atherosclerosis were not addressed in this study. A previous study from Liao’s laboratory showed that macrophage ROCK1 is involved in the pathogenesis for atherosclerosis. Deletion of ROCK1 in bone marrow–derived cells is atheroprotective.

Journal of Vascular Medicine and Surgery is a world-wide peer-reviewed open-access journal which systematically documents several of key developments and medical advances taking place in the field of vascular biology all across the world.

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