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Combination of a peroxisome proliferatoractivated receptor-gamma agonist and an angiotensin II receptor blocker attenuates myocardial fibrosis and dysfunction in type 2 diabetic rats

Authors
 Chi Young Shim  ;  Byeong-Wook Song  ;  Min-Ji Cha  ;  Ki-Chul Hwang  ;  Sungha Park  ;  Geu-Ru Hong  ;  Seok-Min Kang  ;  Jong Eun Lee  ;  Jong-Won Ha  ;  Namsik Chung 
Citation
 JOURNAL OF DIABETES INVESTIGATION, Vol.5(4) : 362-371, 2014 
Journal Title
 JOURNAL OF DIABETES INVESTIGATION 
ISSN
 2040-1116 
Issue Date
2014
Keywords
Angiotensin II receptor blocker ; Diabetic cardiomyopathy ; Peroxisome proliferator‐activated receptor‐gamma agonist
Abstract
AIMS/INTRODUCTION: We aimed to examine the effect of an angiotensin II receptor blocker (ARB), a peroxisome proliferator-activated receptor (PPAR)-gamma agonist, and their combination on myocardial fibrosis and function in type 2 diabetic rats. MATERIALS AND METHODS: Five male Long-Evans Tokushima Otsuka (LETO) rats and 20 male Otsuka Long-Evans Tokushima Fatty (OLETF) rats were used. OLETF rats were assigned to four groups (n = 5 per group) at 28 weeks-of-age: untreated, losartan-treated, rosiglitazone-treated and combination-treated. The ARB, losartan, was administered at a dose of 5 mg/kg/day, and the PPAR-gamma agonist, rosiglitazone, was administered at a dose of 3 mg/kg/day by oral gavage for 12 weeks. Urine and blood samples were collected, and two-dimensional echocardiograms and strain rate imaging were obtained at 28 and 40 weeks. Cytokines were evaluated by reverse transcriptase polymerase chain reaction, and histological analysis was carried out at 40 weeks. RESULTS: At 40 weeks, the global radial strains of the losartan-treated (55.7 ± 4.5%, P = 0.021) and combination-treated groups (59.3 ± 6.7%, P = 0.001) were significantly higher compared with the untreated OLETFs (44.3 ± 10.5%). No difference was observed when compared with LETO rats. Although the rosiglitazone-treated group showed a better metabolic profile than the untreated OLETF group, there was no difference in the global radial strain (49.8 ± 6.0 vs 44.3 ± 10.5, P = 0.402). The expression of pro-inflammatory cytokines, and collagen type I and III were consistently attenuated in the losartan-treated and combination-treated OLETF groups, but not in the rosiglitazone-treated group. CONCLUSIONS: A combination of rosiglitazone and losartan attenuates myocardial fibrosis and dysfunction in type 2 diabetic rats.
Files in This Item:
T201403623.pdf Download
DOI
10.1111/jdi.12153
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Min(강석민) ORCID logo https://orcid.org/0000-0001-9856-9227
Park, Sung Ha(박성하) ORCID logo https://orcid.org/0000-0001-5362-478X
Song, Byeong Wook(송병욱)
Shim, Chi Young(심지영) ORCID logo https://orcid.org/0000-0002-6136-0136
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
Chung, Nam Sik(정남식)
Ha, Jong Won(하종원) ORCID logo https://orcid.org/0000-0002-8260-2958
Hong, Geu Ru(홍그루) ORCID logo https://orcid.org/0000-0003-4981-3304
Hwang, Ki Chul(황기철)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/100084
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