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This Article Full Text Full Text (PDF) All Versions of this Article: 296/5/H1540    most recent 01270.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ying, Z. Articles by Rajagopalan, S. Search for Related Content PubMed PubMed Citation Articles by Ying, Z. Articles by Rajagopalan, S.

Air pollution and cardiac remodeling: a role for RhoA/Rho-kinase

¹Davis Heart Lung Research Institute and ²Division of Environmental Health Sciences, Colleges of Medicine and Public Health, The Ohio State University, Columbus, Ohio; ³Department of Environmental Medicine and Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York; and ⁴Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan

Submitted 8 December 2008 ; accepted in final form 2 March 2009

Exposure to ambient air pollution has been associated with increases in blood pressure. We have previously demonstrated activation of the Rho/Rho kinase pathway in experimental hypertension in rats. In this investigation, we evaluated the effects of particulate matter of <2.5 µm (PM_2.5) exposure on cardiovascular responses and remodeling and tested the effect of Rho kinase inhibition on these effects. C57BL/6 mice were exposed to concentrated ambient PM_2.5 or filtered air for 12 wk followed by a 14-day ANG II infusion in conjunction with fasudil, a Rho kinase antagonist, or placebo treatment. Blood pressure was monitored, followed by analysis of vascular function and ventricular remodeling indexes. PM_2.5 exposure potentiated ANG II-induced hypertension, and this effect was abolished by fasudil treatment. Cardiac and vascular RhoA activation was enhanced by PM_2.5 exposure along with increased expression of the guanine exchange factors (GEFs) PDZ-RhoGEF and p115 RhoGEF in PM_2.5-exposed mice. Parallel with increased RhoA activation, PM_2.5 exposure increased ANG II-induced cardiac hypertrophy and collagen deposition, with these increases being normalized by fasudil treatment. In conclusion, PM_2.5 potentiates cardiac remodeling in response to ANG II through RhoA/Rho kinase-dependent mechanisms. These findings have implications for the chronic cardiovascular health effects of air pollution.

hypertension; vasoconstrictors; angiotensin II