Influence of hypercholesterolemia and hypertension on ischemia-reperfusion induced P-selectin expression.
Risk factors for cardiovascular disease have been shown to exacerbate the inflammatory response and microvascular dysfunction that is normally associated with ischemia-reperfusion. The objective of this study was to determine whether hypercholesterolemia and/or hypertension alter I/R-induced expression of P-selectin in the intestinal vasculature. Male control and hypertensive (HTN) rats were placed on either a normal diet or high cholesterol diet (HCD) for at least 3 weeks resulting in hypercholesterolemia (HC). Ischemia was induced by occlusion of the superior mesenteric artery for 15 min, followed by either 30 min or 4 h of reperfusion. The dual radiolabeled antibody technique was used to quantify the rapid (30 min) and transcription-dependent (4 h) expression of P-selectin. Tissue myeloperoxidase (MPO) was used to quantify neutrophil infiltration. The constitutive (basal) expression of P-selectin did not differ among the experimental groups. Although I/R significantly increased P-selectin expression in control, HC, and HTN+HC, P-selectin expression did not increase in HTN. The HC group exhibited the largest increments in P-selectin expression and tissue MPO after I/R. The increment in P-selectin expression was not significantly attenuated in HC rats that were rendered thrombocytopenic with anti-platelet serum. Treatment with an anti-P-selectin antibody largely prevented the exaggerated MPO increase noted in HC. These findings indicate that hypercholesterolemia in contrast to hypertension enhances the expression of P-selectin in the postischemic intestinal vasculature.
Cerwinka
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Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, P.O. Box 33932, Shreveport, LA 71130-3932, USA.
Granger
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D000818:Animals; D015415:Biomarkers; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D006937:Hypercholesterolemia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D006973:Hypertension / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D008643:Mesentery / Q000098:blood supply; D019007:P-Selectin / Q000096:biosynthesis*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation / Q000502:physiology
D015415:Biomarkers; D019007:P-Selectin; D002784:Cholesterol; D009195:Peroxidase