title: Cardiac fibrosis in diabetic rats: regulation and mechanism of activation of the PPARgamma signal pathway.
abstract: Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a member of the nuclear hormone receptor superfamily which affects organic fibrosis. The aims of the study were to approach the effects of activation of the PPARgamma signal pathway on cardiac fibrosis in diabetic rats, and also the effects on cardiac remodeling and function. Type 1 diabetic models were used in the study. All the animals were divided into 3 groups: I: control group; II: diabetic group; III: diabetes+Pioglitazone (Piog, a PPARgamma ligand) administration group. After 14 weeks of feeding, general condition, fibrosis indices, echocardiography and interventricular pressures parameters were detected. At the 14th week, compared with group I, the hydroxyproline concentration in group II significantly increased, and CO I and III distribution was more obvious by sirius red staining. Reduction of LVSP (left ventricular systolic pressure) and increase of LVEDP (left ventricular end-diastolic pressure) were also significant in group II. But these situations were changed by the administration of Piog in group III. Furthermore, results of RT-PCR and immunohistochemistry showed that Piog administration reduced angiotensin II type 1 receptor (AT1-R) expression in diabetic models. Hence, activation of the PPARgamma signal pathway could repress cardiac fibrosis in diabetic rats, and partly improve cardiac remodeling and function by down-regulating activity of RAS at the receptor level.
authors.affiliation: Department of Cardiology, Beijing Friendship Hospital, Capital Medical University Beijing 100050, PR China.
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Zhao
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Li
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Guo
authors.forename: Lu-Hua
authors.initials: LH
authors.lastname: Shen
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D005355:Fibrosis; D008297:Male; D009206:Myocardium / Q000473:pathology*; D047495:PPAR gamma / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000032:analysis / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D013311:Streptozocin; D016277:Ventricular Function, Left
chemical_list: D047495:PPAR gamma; D044140:Receptor, Angiotensin, Type 1; D013311:Streptozocin