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

Shim CY, Song BW, Cha MJ, Hwang KC, Park S, Hong GR, Kang SM, Lee JE, Ha JW, Chung N - J Diabetes Investig (2013)

Bottom Line: 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%).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.

View Article: PubMed Central - PubMed

Affiliation: Cardiology Division Severance Cardiovascular Hospital Yonsei University College of Medicine Seoul South Korea.

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.

No MeSH data available.


Related in: MedlinePlus

Interposition of collagen fibers in experimental animals. (a–e) Collagen type I. (a) Long‐Evans Tokushima Otsuka rats (LETO). (b) Otsuka Long‐Evans Tokushima Fatty (OLETF) control rats. (c) OLETF rats given losartan. (d) OLETF rats given rosiglitazone. (e) OLETF rats given losartan and rosiglitazone. (f–j) Collagen type III. (f) Long‐Evans Tokushima Otsuka rats (LETO). (g) Otsuka Long‐Evans Tokushima Fatty (OLETF) control rats. (h) OLETF rats given losartan. (i) OLETF rats given rosiglitazone. (j) OLETF rats given losartan and rosiglitazone.
© Copyright Policy - creativeCommonsBy-nc
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4210065&req=5

jdi12153-fig-0003: Interposition of collagen fibers in experimental animals. (a–e) Collagen type I. (a) Long‐Evans Tokushima Otsuka rats (LETO). (b) Otsuka Long‐Evans Tokushima Fatty (OLETF) control rats. (c) OLETF rats given losartan. (d) OLETF rats given rosiglitazone. (e) OLETF rats given losartan and rosiglitazone. (f–j) Collagen type III. (f) Long‐Evans Tokushima Otsuka rats (LETO). (g) Otsuka Long‐Evans Tokushima Fatty (OLETF) control rats. (h) OLETF rats given losartan. (i) OLETF rats given rosiglitazone. (j) OLETF rats given losartan and rosiglitazone.

Mentions: Type I and III collagen interposition in the LV was more prominent in the untreated OLETF controls (Figure 3). In the groups treated with losartan or the combination treatment, collagen interposition was similar to that observed in the LETO rats.


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

Shim CY, Song BW, Cha MJ, Hwang KC, Park S, Hong GR, Kang SM, Lee JE, Ha JW, Chung N - J Diabetes Investig (2013)

Interposition of collagen fibers in experimental animals. (a–e) Collagen type I. (a) Long‐Evans Tokushima Otsuka rats (LETO). (b) Otsuka Long‐Evans Tokushima Fatty (OLETF) control rats. (c) OLETF rats given losartan. (d) OLETF rats given rosiglitazone. (e) OLETF rats given losartan and rosiglitazone. (f–j) Collagen type III. (f) Long‐Evans Tokushima Otsuka rats (LETO). (g) Otsuka Long‐Evans Tokushima Fatty (OLETF) control rats. (h) OLETF rats given losartan. (i) OLETF rats given rosiglitazone. (j) OLETF rats given losartan and rosiglitazone.
© Copyright Policy - creativeCommonsBy-nc
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4210065&req=5

jdi12153-fig-0003: Interposition of collagen fibers in experimental animals. (a–e) Collagen type I. (a) Long‐Evans Tokushima Otsuka rats (LETO). (b) Otsuka Long‐Evans Tokushima Fatty (OLETF) control rats. (c) OLETF rats given losartan. (d) OLETF rats given rosiglitazone. (e) OLETF rats given losartan and rosiglitazone. (f–j) Collagen type III. (f) Long‐Evans Tokushima Otsuka rats (LETO). (g) Otsuka Long‐Evans Tokushima Fatty (OLETF) control rats. (h) OLETF rats given losartan. (i) OLETF rats given rosiglitazone. (j) OLETF rats given losartan and rosiglitazone.
Mentions: Type I and III collagen interposition in the LV was more prominent in the untreated OLETF controls (Figure 3). In the groups treated with losartan or the combination treatment, collagen interposition was similar to that observed in the LETO rats.

Bottom Line: 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%).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.

View Article: PubMed Central - PubMed

Affiliation: Cardiology Division Severance Cardiovascular Hospital Yonsei University College of Medicine Seoul South Korea.

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.

No MeSH data available.


Related in: MedlinePlus