TY - JOUR
T1 - Nitric oxide-releasing aspirin decreases vascular injury by reducing inflammation and promoting apoptosis
AU - Yu, Jun
AU - Rudic, Radu Daniel
AU - Sessa, William C.
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health (RO1 HL57665, HL61371, and HL64793 to WCS). Address reprint requests to: Dr. William C. Sessa, Department of Pharmacology and Program in Vascular Cell Signaling and Therapeutics, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536. E-mail: william.sessa@yale.edu
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0036311339&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036311339&partnerID=8YFLogxK
U2 - 10.1097/01.LAB.0000018828.61722.BD
DO - 10.1097/01.LAB.0000018828.61722.BD
M3 - Article
C2 - 12118084
AN - SCOPUS:0036311339
SN - 0023-6837
VL - 82
SP - 825
EP - 832
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 7
ER -