Original ContributionPlatelet-associated NAD(P)H oxidase contributes to the thrombogenic phenotype induced by hypercholesterolemia
Section snippets
Animals
Male wild-type C57BL/6J (WT), B6.129S6-Cybbtm1Din/J (gp91phox−/−), and breeder stocks for C57BL/6-Tg(SOD1)3Cje/J (SOD-TgN) mice on a C57BL/6 background were obtained from The Jackson Laboratory (Bar Harbor, ME, USA). The SOD-TgN mice were identified by qualitative demonstration of Cu,Zn-SOD using nondenaturing gel electrophoresis followed by nitroblue tetrazolium staining. Nontransgenic littermates were used as controls (SOD-nonTgN). At 6–8 weeks of age the mice were placed on either a normal
Blood cholesterol concentration and wall shear rate
Placement of WT and mutant mice on a cholesterol-enriched diet for 2 weeks led to a two- to threefold increase in blood cholesterol concentration, with no statistical difference between the HC groups (Table 1). Wall shear rate was comparable between all groups examined, suggesting this was not a factor in producing the differences in blood cell recruitment. Furthermore, no differences in circulating leukocyte or platelet counts were noted between any of the experimental groups.
Leukocyte recruitment in postcapillary venules
Discussion
Hypercholesterolemia elicits an inflammatory response in the microvasculature of many organs, including skeletal muscle, intestine, brain, and mesentery [3], [4], [11], [12], [14]. This inflammatory response is characterized by endothelial dysfunction/activation and manifests as impaired endothelium-dependent vasodilation in arterioles [3], [4] and leukocyte and platelet recruitment in postcapillary venules [4], [14], [22]. In hypercholesterolemic humans and animals, oxidative stress has been
Acknowledgments
This work was supported by a grant from the National Heart, Lung, and Blood Institute (HL26441). The authors thank Dr. Kevin Pruitt and Ms. Sherry Jackson for their technical assistance.
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