Deficiency of ROCK1 in bone marrow-derived cells protects against atherosclerosis in LDLR-/- mice

Hong Wei Wang, Ping Yen Liu, Naotsugu Oyama, Yoshiyuki Rikitake, Shiro Kitamoto, Jonathan Gitlin, James K. Liao, William A. Boisvert

研究成果: Article同行評審

66 引文 斯高帕斯(Scopus)

摘要

Rho kinases (ROCKs) are serine-threonine protein kinases that regulate the actin cytoskeleton. Recent studies suggest that ROCKs also play an important role in cardiovascular disease. However, the isoform- and tissue-specific role of ROCKs in mediating this process is unknown. Using homologous recombination, we generated mutant mice harboring alleles with homozygous deletion of ROCK1 (ROCK1-/-). Most ROCK1-/- mice die perinatally. However, a few ROCK1-/- mice survive to adulthood, are phenotypically normal, and have no apparent compensatory changes in ROCK2. Using these ROCK1 -/- mice, we show that ROCK1 in bone marrow-derived macrophages is critical to the development of atherosclerosis, in part, by mediating foam cell formation and macrophage chemotaxis. Lipid accumulation and atherosclerotic lesions were reduced in atherosclerosis-prone LDLR-/- mice, whose bone marrows have been replaced with bone marrows derived from ROCK1 -/- mice. Bone marrow-derived ROCK1-deficient macrophages exhibited impaired chemotaxis to monocyte chemotactic protein-1 and showed reduced ability to take up lipids and to develop into foam cells when exposed to modified low-density lipoprotein. These findings indicate that ROCK1 in bone marrow-derived cells is a critical mediator of atherogenesis and suggest that macrophage ROCK1 may be an important therapeutic target for vascular inflammation and atherosclerosis.

原文English
頁(從 - 到)3561-3570
頁數10
期刊FASEB Journal
22
發行號10
DOIs
出版狀態Published - 2008 10月

All Science Journal Classification (ASJC) codes

  • 生物技術
  • 生物化學
  • 分子生物學
  • 遺傳學

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