The role of p21-activated kinase in the initiation of atherosclerosis

BMC Cardiovascular Disorders

Research Article

P Debnath¹  J Sanders¹  K A Jhaveri¹  M A Schwartz²  J Chernoff³ 

[1] Department of Microbiology, University of Virginia, Cardiovascular Research Center, Charlottesville, Virginia, USA;Department of Microbiology, University of Virginia, Cardiovascular Research Center, Charlottesville, Virginia, USA;Yale Cardiovascular Research Center, 300 George St, 06511, New Haven, CT, USA;Division of Oncology Research, Fox Chase Cancer Center, Buckingham, Pennsylvania, USA;

关键词: Fluid shear stress;    Endothelial cells;    Vascular inflammation;    Fibronectin;   

DOI  :  10.1186/1471-2261-12-55

 received in 2012-03-09, accepted in 2012-07-23,  发布年份 2012

来源: Springer

【 摘 要 】

Backgroundp21-activated kinase (PAK) has been implicated in the inflammatory activation of endothelial cells by disturbed fluid shear stress, which is the initiating stimulus in atherosclerosis. The study addresses whether PAK1 contributes to inflammatory marker expression in endothelial cells at atherosclerosis-susceptible regions of arteries in vivo.MethodAortas from WT and PAK1-/- C57BL/6J mice on a normal chow diet were fixed, dissected and processed for immunohistochemistry using a panel of inflammatory markers. We visualized and quantified staining in the endothelium at the greater and lesser curvatures of the arch of aorta, as atherosclerosis-resistant and susceptible regions, respectively.ResultsFibronectin, VCAM-1 and the activated RelA NF-κB subunit were localized to the lesser curvature and decreased in PAK1-/- mice. The activated RelB NF-κB subunit was also localized to the lesser curvature but was increased in PAK1-/- mice. Low levels of staining for ICAM-1 and the monocyte/macrophage marker Mac2 indicated that overall inflammation in this tissue was minimal.ConclusionThese data show that PAK1 has a significant pro-inflammatory function at atherosclerosis-prone sites in vivo. These effects are seen in young mice with very low levels of inflammation, suggesting that inflammatory activation of the endothelium is primarily biomechanical. Activation involves NF-κB, expression of leukocyte recruitment receptors and fibronectin deposition. These results support and extend in vitro studies demonstrating that PAK contributes to activation of inflammatory pathways in endothelial cells by fluid shear stress.

【 授权许可】

Unknown   
© Jhaveri et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.