Pioglitazone Attenuates Vascular Fibrosis in Spontaneously Hypertensive Rats
Objective. We sought to investigate whether the peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand pioglitazone can attenuate vascular fibrosis in spontaneously hypertensive rats (SHRs) and explore the possible molecular mechanisms. Methods. SHRs (8-week-old males) were randomly divided in...
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| Language: | English |
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Wiley
2012-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2012/856426 |
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| author | Dengfeng Gao Ning Ning Guanghua Hao Xiaolin Niu |
| author_facet | Dengfeng Gao Ning Ning Guanghua Hao Xiaolin Niu |
| author_sort | Dengfeng Gao |
| collection | DOAJ |
| description | Objective. We sought to investigate whether the peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand pioglitazone can attenuate vascular fibrosis in spontaneously hypertensive rats (SHRs) and explore the possible molecular mechanisms. Methods. SHRs (8-week-old males) were randomly divided into 3 groups (n=8 each) for treatment: pioglitazone (10 mg/kg/day), hydralazine (25 mg/kg/day), or saline. Normal male Wistar Kyoto (WKY) rats (n=8) served as normal controls. Twelve weeks later, we evaluated the effect of pioglitazone on vascular fibrosis by Masson’s trichrome and immunohistochemical staining of collagen III and real-time RT-PCR analysis of collagen I, III and fibronectin mRNA.Vascular expression of PPAR-γ and connective tissue growth factor (CTGF) and transforming growth factor-β (TGF-β) expression were evaluated by immunohistochemical staining, western blot analysis, and real-time RT-PCR. Results. Pioglitazone and hydralazine treatment significantly decreased systolic blood pressure in SHRs. Masson’s trichrome staining for collagen III and real-time RT-PCR analysis of collagen I, III and fibronectin mRNA indicated that pioglitazone significantly inhibited extracellular matrix production in the aorta. Compared with Wistar Kyoto rats, SHRs showed significantly increased vascular CTGF expression. Pioglitazone treatment significantly increased PPAR-γ expression and inhibited CTGF expression but had no effect on TGF-β expression. Conclusions. The results indicate that pioglitazone attenuated vascular fibrosis in SHRs by inhibiting CTGF expression in a TGF-β-independent mechanism. |
| format | Article |
| id | doaj-art-084586b06ba04946a8cdaf6c37b3c7e2 |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-084586b06ba04946a8cdaf6c37b3c7e22025-02-03T01:23:59ZengWileyPPAR Research1687-47571687-47652012-01-01201210.1155/2012/856426856426Pioglitazone Attenuates Vascular Fibrosis in Spontaneously Hypertensive RatsDengfeng Gao0Ning Ning1Guanghua Hao2Xiaolin Niu3Department of Cardiology, The Second Affiliated Hospital, Xi’an Jiaotong University School of Medicine, Shaanxi, Xi’an 710004, ChinaDepartment of Nuclear Medicine, The Second Affiliated Hospital, Xi’an Jiaotong University School of Medicine, Shaanxi, Xi’an 710004, ChinaDepartment of Cardiology, The Second Affiliated Hospital, Xi’an Jiaotong University School of Medicine, Shaanxi, Xi’an 710004, ChinaDepartment of Cardiology, The Second Affiliated Hospital, Xi’an Jiaotong University School of Medicine, Shaanxi, Xi’an 710004, ChinaObjective. We sought to investigate whether the peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand pioglitazone can attenuate vascular fibrosis in spontaneously hypertensive rats (SHRs) and explore the possible molecular mechanisms. Methods. SHRs (8-week-old males) were randomly divided into 3 groups (n=8 each) for treatment: pioglitazone (10 mg/kg/day), hydralazine (25 mg/kg/day), or saline. Normal male Wistar Kyoto (WKY) rats (n=8) served as normal controls. Twelve weeks later, we evaluated the effect of pioglitazone on vascular fibrosis by Masson’s trichrome and immunohistochemical staining of collagen III and real-time RT-PCR analysis of collagen I, III and fibronectin mRNA.Vascular expression of PPAR-γ and connective tissue growth factor (CTGF) and transforming growth factor-β (TGF-β) expression were evaluated by immunohistochemical staining, western blot analysis, and real-time RT-PCR. Results. Pioglitazone and hydralazine treatment significantly decreased systolic blood pressure in SHRs. Masson’s trichrome staining for collagen III and real-time RT-PCR analysis of collagen I, III and fibronectin mRNA indicated that pioglitazone significantly inhibited extracellular matrix production in the aorta. Compared with Wistar Kyoto rats, SHRs showed significantly increased vascular CTGF expression. Pioglitazone treatment significantly increased PPAR-γ expression and inhibited CTGF expression but had no effect on TGF-β expression. Conclusions. The results indicate that pioglitazone attenuated vascular fibrosis in SHRs by inhibiting CTGF expression in a TGF-β-independent mechanism.http://dx.doi.org/10.1155/2012/856426 |
| spellingShingle | Dengfeng Gao Ning Ning Guanghua Hao Xiaolin Niu Pioglitazone Attenuates Vascular Fibrosis in Spontaneously Hypertensive Rats PPAR Research |
| title | Pioglitazone Attenuates Vascular Fibrosis in Spontaneously Hypertensive Rats |
| title_full | Pioglitazone Attenuates Vascular Fibrosis in Spontaneously Hypertensive Rats |
| title_fullStr | Pioglitazone Attenuates Vascular Fibrosis in Spontaneously Hypertensive Rats |
| title_full_unstemmed | Pioglitazone Attenuates Vascular Fibrosis in Spontaneously Hypertensive Rats |
| title_short | Pioglitazone Attenuates Vascular Fibrosis in Spontaneously Hypertensive Rats |
| title_sort | pioglitazone attenuates vascular fibrosis in spontaneously hypertensive rats |
| url | http://dx.doi.org/10.1155/2012/856426 |
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