TY - JOUR
T1 - Activation of the peroxisome proliferator-activated receptor α protects against myocardial ischaemic injury and improves endothelial vasodilatation
AU - Tabernero, Antonia
AU - Schoonjans, Kristina
AU - Jesel, Laurence
AU - Carpusca, Irina
AU - Auwerx, Johan
AU - Andriantsitohaina, Ramaroson
PY - 2002/4/9
Y1 - 2002/4/9
N2 - Background: The peroxisome proliferator-activated receptor α (PPARα) plays an important role in the metabolism of lipoproteins and fatty acids, and seems to protect against the development of atherosclerosis. To evaluate the possible protective role of PPARα on cardiovascular function, the effect of the PPARα agonist, fenofibrate was assessed with respect to ischaemia/reperfusion injury and endothelial function in mice. Results: Fenofibrate treatment reduces myocardial infarction size and improves post-ischaemic contractile dysfunction. Hearts from PPARα null mice exhibit increased susceptibility to ischaemic damages and were refractory to protection by fenofibrate treatment suggesting that the beneficial effects of fenofibrate were mediated via PPARα. Furthermore, fenofibrate improves endotheliumand nitric oxide-mediated vasodilatation in aorta and mesenteric vascular bed. A decreased inhibitory effect of reactive oxygen species in the vessel wall accounts for enhanced endothelial vasodilatation. However, the latter cannot be explained by an increase in nitric oxide synthase expression nor by an increase sensitivity of the arteries to nitric oxide. Conclusions: Altogether the present data suggest that fenofibrate exerts cardioprotective effect against ischaemia and improves nitric oxide-mediated response probably by enhancing antioxidant capacity of the vessel wall. These data underscore new therapeutic perspectives for PPARα agonists in ischaemic myocardial injury and in cardiovascular diseases associated with endothelial dysfunction.
AB - Background: The peroxisome proliferator-activated receptor α (PPARα) plays an important role in the metabolism of lipoproteins and fatty acids, and seems to protect against the development of atherosclerosis. To evaluate the possible protective role of PPARα on cardiovascular function, the effect of the PPARα agonist, fenofibrate was assessed with respect to ischaemia/reperfusion injury and endothelial function in mice. Results: Fenofibrate treatment reduces myocardial infarction size and improves post-ischaemic contractile dysfunction. Hearts from PPARα null mice exhibit increased susceptibility to ischaemic damages and were refractory to protection by fenofibrate treatment suggesting that the beneficial effects of fenofibrate were mediated via PPARα. Furthermore, fenofibrate improves endotheliumand nitric oxide-mediated vasodilatation in aorta and mesenteric vascular bed. A decreased inhibitory effect of reactive oxygen species in the vessel wall accounts for enhanced endothelial vasodilatation. However, the latter cannot be explained by an increase in nitric oxide synthase expression nor by an increase sensitivity of the arteries to nitric oxide. Conclusions: Altogether the present data suggest that fenofibrate exerts cardioprotective effect against ischaemia and improves nitric oxide-mediated response probably by enhancing antioxidant capacity of the vessel wall. These data underscore new therapeutic perspectives for PPARα agonists in ischaemic myocardial injury and in cardiovascular diseases associated with endothelial dysfunction.
UR - http://www.scopus.com/inward/record.url?scp=2642581745&partnerID=8YFLogxK
U2 - 10.1186/1471-2210-2-10
DO - 10.1186/1471-2210-2-10
M3 - Article
C2 - 11940253
AN - SCOPUS:2642581745
SN - 1471-2210
VL - 2
JO - BMC Pharmacology
JF - BMC Pharmacology
M1 - 10
ER -