Peroxisome proliferator-activated receptor-gamma agonists attenuate angiotensin II-induced collagen type I expression in adventitial fibroblasts

Jia Zhang, Ning-Yuan Fang, Ping-Jin Gao, Ling-Yun Wu, Wei-Qing Han, Shu-Jie Guo, Wei-Li Shen, Ding-Liang Zhu
Clinical and Experimental Pharmacology & Physiology 2008, 35 (1): 72-7
1. Angiotensin (Ang) II-mediated oxidative stress may be important in enhanced adventitial fibroblast collagen formation. The aim of the present study was to test whether PPAR-gamma agonists 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ2) and pioglitazone could alter AngII-induced collagen type I formation in vascular adventitial fibroblasts via reactive oxygen species (ROS). 2. Vascular adventitial fibroblasts were isolated from rat thoracic aortas of male Sprague-Dawley rats and treated with different concentrations of AngII for different periods of time. The expression of collagen type I induced by AngII was examined by western blot. Expression of PPAR-gamma mRNA was examined by reverse transcription-polymerase chain reaction (RT-PCR). Intracellular ROS generation was measured by flow cytometry. Activation of transcription factors nuclear factor (NF)-kappaB and activator protein (AP)-1 was assessed by an electrophoretic mobility shift assay. 3. Angiotensin II increased expression of collagen type I in a time- and dose-dependent manner in adventitial fibroblasts. In addition, AngII stimulated intracellular generation of ROS in adventitial fibroblasts. Pretreatment of cells with 15d-PGJ2 and pioglitazone attenuated collagen type I expression and generation of ROS induced by AngII, respectively. Moreover, we observed that N-acetylcysteine inhibited collagen type I expression induced by AngII as did the PPAR-gamma agonists. Angiotensin II treatment activated the redox-sensitive transcription factors NF-kappaB and AP-1, whereas pretreatment with 15d-PGJ2 and pioglitazone reduced the AngII-induced DNA-binding activity of NF-kappaB but not AP-1. 4 Our data demonstrate that the PPAR-gamma agonists 15d-PGJ2 and pioglitazone attenuate AngII-mediated collagen type I expression in adventitial fibroblasts, which may be mediated by the modulation of ROS release and the redox-sensitive transcription factor NF-kappaB.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"