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Protective effects of PPAR y agonists against ischemia-reperfusion damage to heart are
attributed to a number of factors such as inhibition of fUN-kinase, attenuation of INOS,
inhibition of NF-kB and decrease in TNF-c¿ and TGF-B signaling (I\4olavi et al. 2005;
Shiomi et al. 2002;'Wayman et al. 2002).
The usage of PPAR y agonists in clinical setting is currently limited due to the
reports of the development of peripheral edema and increased occurrence of congestive
heart failure in some patients (Krentz et al. 2000; Wooltron E 2002). Another setback for
the usage of PPAR y agonists therapy in patients is the fact that of PPAR y receptors are
still not definitely identified in heart tissue which questions their direct effects on heart
tissue and implies the existence of an indirect protective mechanisms Q.{ikolaidis and
Levine 2004).
The usage of PPAR a agonists was also shown to cause the protection against
heart failure. It is suggested that the usage of PPAR cr agonists in heart failure may reactivate
the metabolism of free fatty acids by heart muscle thus preventing the
detrimental effects of glucose utilization. The usage of PPAR a agonist was shown to be
beneficial against the myocardial remodeling process induced by pressure-overload
phenomenon (Ogata et aL.2002). The same study has shown that treatment with PPAR a
agonist-fenofibrate was able to prevent the increase in the expression of prepro-ET-i and
collagen type I and type II mRNA induced by the pressure overload (Ogata et al.2002) .
This coincided with a decrease in interstitial and peri-vascular cardiac fibrosis (Ogata et
al. 2002). The usage of fenofibrate was also shown to have a benef,rcial effects of
inflammation and collage deposition in hearts of ANG Il-infused rats (Diep et al.2002a).
The study using a cre-loxP-mediated cardiomyocyte-restricted deletion of PPAR p/ô in
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