title: Fasudil, a Rho‑kinase inhibitor, prevents intima‑media thickening in a partially ligated carotid artery mouse model: Effects of fasudil in flow‑induced vascular remodeling.
abstract: Vascular remodeling in response to hemodynamic alterations is a physiological process that requires coordinated signaling between endothelial, inflammatory and vascular smooth muscle cells (VSMCs). Extensive experimental and clinical studies have indicated the critical role of the Ras homolog gene family, member A/Rho‑associated kinase (ROCK) signaling pathway in the pathogenesis of cardiovascular disease, where ROCK activation has been demonstrated to promote inflammation and remodeling through inducing the expression of proinflammatory cytokines and adhesion molecules in endothelial cells and VSMCs. However, the role of ROCK in flow‑induced vascular remodeling has not been fully defined. The current study aimed to investigate the effect of the ROCK signaling pathway in flow‑induced vascular remodeling by comparing the responses to partial carotid artery ligation in mice treated with fasudil (a ROCK inhibitor) and untreated mice. Intima‑media thickness and neointima formation were evaluated by morphology. VSMC proliferation and inflammation of the vessel wall were assessed by immunohistochemistry. In addition, the expression levels of ROCK and the downstream effectors of ROCK, myosin light chain (MLC) and phosphorylated‑MLC (p‑MLC), were quantified by western blot analysis. Following a reduction in blood flow, ROCK1 and p‑MLC expression increased in the untreated left common carotid arteries (LCA). Fasudil‑treated mice developed a significantly smaller intima‑media thickness compared with the untreated mice. Quantitative immunohistochemistry of the fasudil‑treated LCA indicated that there was a reduction in proliferation when compared with untreated vessels. There were fewer CD45+ cells observed in the fasudil‑treated LCA compared with the untreated LCA. In conclusion, the expression of ROCK was enhanced in flow‑induced carotid artery remodeling and ROCK inhibition as a result of fasudil treatment may attenuate flow‑induced carotid artery remodeling.
authors.affiliation: Department of Vascular Surgery, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Vascular Surgery, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Vascular Surgery, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Fu
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Vascular Surgery, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Qingle
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Vascular Surgery, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Chenyang
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Tianjin Medical University, Tianjin 300000, P.R. China.
authors.forename: Yankui
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Vascular Surgery, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Vascular Surgery, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhang
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058426:Neointima / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D066253:Vascular Remodeling / Q000187:drug effects*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C049347:fasudil