Nitric oxide-releasing aspirin decreases vascular injury by reducing inflammation and promoting apoptosis.
Endothelial dysfunction, defined as a deficit in the bioavailability of nitric oxide (NO), occurs as sequelae of many vascular diseases; however, the utility of supplementing NO to obviate the extent of disease is understudied. Here, we examined if prolonged treatment with an NO-releasing form of aspirin (NO-ASA) can influence neointimal remodeling of femoral arteries of hypercholesterolemic ApoE (-/-) mice. Treatment of ApoE (-/-) mice with NO-ASA, but not aspirin (ASA), improved neointimal remodeling post-injury. NO-ASA treatment increased lumen diameters and reduced intimal-to-medial ratios of injured femoral arteries compared with ASA- or vehicle-treated mice. The reduction in lumen diameter in NO-ASA-treated mice was associated with a marked reduction in CD45-positive inflammatory cells and an increased number of TUNEL-positive cells. Thus, NO-ASA, by virtue of releasing NO, can reduce vascular inflammation and promote apoptosis during vascular remodeling associated with neointimal thickening.
Department of Pharmacology and Program in Vascular Cell Signaling and Therapeutics,Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
Jun
J
Yu
Radu Daniel
RD
Rudic
William C
WC
Sessa
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D017209:Apoptosis / Q000187:drug effects*; D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood*; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*
D001057:Apolipoproteins E; D010975:Platelet Aggregation Inhibitors; C098312:nitroxy-butyl-acetylsalicylic acid; D002784:Cholesterol; D001241:Aspirin