title: Rho kinase inhibition by fasudil has anti-inflammatory effects in hypercholesterolemic rats.
abstract: Inhibition of Rho kinase (ROCK) ameliorates many cardiovascular dysfunctions. The aim of the current study is to investigate the anti-inflammatory effects of fasudil, a selective ROCK inhibitor, on high cholesterol diet-induced hypercholesterolemic rats and its possible mechanisms. In hypercholesterolemic rats, we found the serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and several inflammatory markers including interleukin (IL)-8, IL-6, C-reaction protein (CRP) and soluble intercellular adhesion molecule (sICAM)-1 significantly elevated, while those of high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) decreased. Moreover, mRNA expressions of ROCK and nuclear factor-kappa B (NF-κB) and activity of ROCK in thoracic aorta were greatly up-regulated. Remarkably, administrating fasudil (10, 30 mg/kg per day) or simvastatin (10 mg/kg per day) to hypercholesterolemic rats for 2 weeks, activation of ROCK and NF-κB in thoracic aorta were suppressed, status of dyslipidemia were improved and inflammatory markers lowered. From the histopathological examination, fasudil treatment was found to lessen the thickening noted in the aortic intima and media of the hypercholesterolemic rats. These results suggested fasudil-induced inhibition of ROCK may improve lipid metabolism and has anti-inflammatory effect, which might expand the clinical application of fasudil as a new therapy for hypercholesterolemia and preventing the development of atherosclerosis.
authors: Department of Pharmacology, School of Basic Medicine, Hebei Medical University, No. 326 Xinshi South Road, Shijiazhuang, Hebei, China.
authors: Zhihong
authors: Z
authors: Ma
authors: Jianping
authors: J
authors: Zhang
authors: Rongpin
authors: R
authors: Du
authors: Ensheng
authors: E
authors: Ji
authors: Li
authors: L
authors: Chu
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000473:pathology; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D018836:Inflammation Mediators / Q000097:blood*; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use; D017539:Tunica Intima / Q000187:drug effects; D017540:Tunica Media / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D008055:Lipids; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D019821:Simvastatin; D054460:rho-Associated Kinases; C049347:fasudil