The effects of a PPARalpha agonist on myocardial damage in obese diabetic mice with heart failure.
Recent studies have confirmed that PPARalpha agonists have not brought the anticipated benefits to patients with type 2 diabetes and potentially fatal heart disease. We hypothesized that such agonists may have a cardio-suppressive effect in treating such disorders, therefore, we inoculated diabetic KKAy mice with encephalomyocarditis virus (EMCv) to induce a diabetic model with severe myocardial damage. WY14643, a potent PPARalpha agonist, was administered intraperitoneally either simultaneously (WY14643-late group) or 3 days before viral inoculation (WY14643-early group). WY14643-treated mice, especially those in the WY14643-early group, had higher mortality than those in the vehicle-treated group (vehicle) in the first 5 days after EMCv inoculation. However, the survival rate in the vehicle group decreased rapidly after day 4 and was the lowest of all 3 groups by day 9. The WY14643-treated mice showed reduced body weight and blood glucose, improved myocardial pathological changes, lower cardiac TNF-alpha expression, and significantly higher adiponectin expression, whereas the LW/LC ratio was lower and cardiac UCP3 mRNA expression higher in the WY14643 treatment groups than in the vehicle group on day 4. WY14643 therefore has cardioprotective and cardio-suppressive effects when used to treat EMCv-induced myocarditis in diabetic mice. The cardioprotective effect may be due to its anti-inflammatory properties and its ability to increase cardiac adiponectin expression, whereas the reduced cardiac efficiency may be due to its enhancement of cardiac UCP3 mRNA expression.
Chen
Rui
R
Department of General Medicine, Himi City Hospital, Kanazawa Medical University, Toyama, Japan.
Liang
Fengxia
F
Morimoto
Shigeto
S
Li
Qian
Q
Moriya
Junji
J
Yamakawa
Jun-ichi
J
Takahashi
Takashi
T
Iwai
Kunimitsu
K
Kanda
Tsugiyasu
T
D052242:Adiponectin / Q000502:physiology; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D008820:Mice, Obese; D024101:Mitochondrial Proteins / Q000502:physiology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D047493:PPAR alpha / Q000819:agonists; D020025:Peroxisome Proliferators / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*
D052242:Adiponectin; D024101:Mitochondrial Proteins; D047493:PPAR alpha; D020025:Peroxisome Proliferators; D011743:Pyrimidines; C006253:pirinixic acid