Peroxisome proliferator activated-receptor agonism and left ventricular remodeling in mice with chronic myocardial infarction.
1. Peroxisome proliferator activated receptor gamma (PPARgamma) has been implicated in several cellular pathways assumed to beneficially affect heart failure progression. In contrast, population-based studies demonstrate an increased incidence of heart failure in patients treated with PPARgamma agonists. Therefore, we examined the effect of pioglitazone, a PPARgamma agonist, on chronic left ventricular remodeling after experimental myocardial infarction (MI) in mice. 2. Mice were treated with placebo or pioglitazone (20 mg x kg(-1) by gavage) from week 1 to week 6 after ligation of the left anterior descending artery. Serial transthoracic echocardiography was performed at weeks 1, 3, and 6. 3. Over 6 weeks, there was no difference in mortality (placebo 12%, pioglitazone 10%). Echocardiography showed significant left ventricular dilatation in animals with MI (week 6, end-systolic area, placebo sham 9.6+/-1.3 vs placebo MI 14.4+/-2.5 mm(2)). However, there was no difference between the placebo and pioglitazone groups (week 6, end-systolic area, pioglitazone MI 14.8+/-2.9 mm(2), P=NS vs placebo). 4. Moreover, there were no changes in metabolic parameters, inflammation, and collagen deposition. Endothelial function in the aorta was not changed by PPARgamma activation. 5. In conclusion, PPARgamma activation did not adversely affect left ventricular remodeling and survival in mice with chronic MI. However, we were also not able to identify a protective effect of pioglitazone.
Frantz
Stefan
S
Medizinische Klinik der Universität Würzburg, Germany. s.frantz@mail.uni-wuerzburg.de
Hu
Kai
K
Widder
Julian
J
Bayer
Barbara
B
Witzel
Catharina Clara
CC
Schmidt
Isabel
I
Galuppo
Paolo
P
Strotmann
Jörg
J
Ertl
Georg
G
Bauersachs
Johann
J
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D001786:Blood Glucose; D001835:Body Weight / Q000187:drug effects; D002908:Chronic Disease; D003094:Collagen / Q000737:chemistry; D003331:Coronary Vessels / Q000293:injuries; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004452:Echocardiography / Q000379:methods; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D018836:Inflammation Mediators / Q000097:blood; D007441:Intubation, Gastrointestinal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000209:etiology / Q000401:mortality / Q000503:physiopathology*; D009206:Myocardium / Q000737:chemistry / Q000648:ultrastructure; D009929:Organ Size / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology*
D001786:Blood Glucose; D016207:Cytokines; D019332:Endothelin-1; D018836:Inflammation Mediators; D045162:Thiazolidinediones; D014280:Triglycerides; D010656:Phenylephrine; D003094:Collagen; D000077205:Pioglitazone