QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.105.090993v1 315/3/1020    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Johns, D. G. Articles by Macphee, C. H. Search for Related Content PubMed PubMed Citation Articles by Johns, D. G. Articles by Macphee, C. H.

CARDIOVASCULAR

Rosiglitazone Protects against Ischemia/Reperfusion-Induced Leukocyte Adhesion in the Zucker Diabetic Fatty Rat

Departments of Vascular Biology and Thrombosis (D.G.J., Z.A., S.A.D., C.H.M.), Investigative Support and Cardiac Biology (M.E., A.O., M.C., S.G.), Cardiovascular and Urogenital Centre for Excellence in Drug Discovery, and Scientific Strategy (S.A.S.), GlaxoSmithKline, King of Prussia, Pennsylvania

Increased susceptibility to atherosclerosis increases the risk of mortality in type 2 diabetic patients. Leukocyte adhesion to the endothelium is a critical step in atherogenesis. In addition to its insulin-sensitizing effects, rosiglitazone (RSG) possesses anti-inflammatory properties. However, the effects of RSG on the initial phase of leukocyte recruitment (rolling, adhesion) have not been studied in vivo. This study tested the hypothesis that RSG treatment of Zucker diabetic fatty (ZDF) rats inhibits ischemia/reperfusion-induced leukocyte adhesion to the endothelium. Male ZDF rats (16 weeks) were treated with RSG (3 mg/kg/day, p.o.) 7 days before experimentation. Leukocyte-endothelial interactions in cremaster venules were recorded using intravital microscopy prior to 30 min of ischemia and during a 90-min reperfusion period. Although blood pressure, plasma glucose, and insulin were not different between treatment groups, RSG treatment was associated with reduced leukocyte rolling and inhibition of leukocyte adhesion throughout the reperfusion period (P < 0.01). Cremaster mRNA expression of vascular cell adhesion molecule-1 (VCAM-1) was reduced by 35% in RSG-treated animals (P < 0.01), whereas P- and E-selectin and intercellular adhesion molecule-1 (ICAM-1) were unchanged. Immunostaining for P-selectin, E-selectin, and VCAM-1 was reduced by 21, 61, and 50%, respectively (for all, P < 0.05), in RSG-treated animals. Inhibition of ischemia/reperfusion-induced leukocyte adhesion might contribute to the utility of RSG as a therapy for vascular disease.

Address correspondence to: Dr. Douglas G. Johns, Cardiovascular and Urogenital Centre for Excellence in Drug Discovery, Vascular Biology and Thrombosis, GlaxoSmithKline, 709 Swedeland Rd, UW2510, King of Prussia, PA 19406. E-mail: douglas.g.johns{at}gsk.com

This article has been cited by other articles:

				J.-Y. Han, Y. Horie, J.-Y. Fan, K. Sun, J. Guo, S. Miura, and T. Hibi Potential of 3,4-dihydroxy-phenyl lactic acid for ameliorating ischemia-reperfusion-induced microvascular disturbance in rat mesentery Am J Physiol Gastrointest Liver Physiol, January 1, 2009; 296(1): G36 - G44. [Abstract] [Full Text] [PDF]

				E. D. Abel, S. E. Litwin, and G. Sweeney Cardiac Remodeling in Obesity Physiol Rev, April 1, 2008; 88(2): 389 - 419. [Abstract] [Full Text] [PDF]

				S. Boudina and E. D. Abel Diabetic Cardiomyopathy Revisited Circulation, June 26, 2007; 115(25): 3213 - 3223. [Abstract] [Full Text] [PDF]

				J. D. Knudson, G. M. Dick, and J. D. Tune Adipokines and Coronary Vasomotor Dysfunction Experimental Biology and Medicine, June 1, 2007; 232(6): 727 - 736. [Abstract] [Full Text] [PDF]