Angiotensin II Regulation of Collagen Type I Expression in Cardiac Fibroblasts

Hypertension - Tập 44 Số 5 - Trang 655-661 - 2004
Kui Chen1, Jiawei Chen2, Dayuan Li3, Xingjian Zhang4, Jawahar L. Mehta5
1Kui Chen From the Departments of Internal Medicine and Physiology and Biophysics, University of Arkansas for Medical Sciences, and the Central Arkansas Veterans Healthcare System, Little Rock.
2Jiawei Chen From the Departments of Internal Medicine and Physiology and Biophysics, University of Arkansas for Medical Sciences, and the Central Arkansas Veterans Healthcare System, Little Rock.
3Dayuan Li From the Departments of Internal Medicine and Physiology and Biophysics, University of Arkansas for Medical Sciences, and the Central Arkansas Veterans Healthcare System, Little Rock.
4Xingjian Zhang From the Departments of Internal Medicine and Physiology and Biophysics, University of Arkansas for Medical Sciences, and the Central Arkansas Veterans Healthcare System, Little Rock.
5Jawahar L. Mehta From the Departments of Internal Medicine and Physiology and Biophysics, University of Arkansas for Medical Sciences, and the Central Arkansas Veterans Healthcare System, Little Rock.

Tóm tắt

Angiotensin II (Ang II)–mediated stimulation of fibroblast growth and collagen type I synthesis is believed to be an important component of the cardiac remodeling process in hypertension and chronic ischemia. Ang II–mediated oxidative stress could be important in enhanced fibroblast growth and collagen formation. Accordingly, we postulated that the PPAR-γ ligand, pioglitazone, which is known to modulate oxidative stress, would alter Ang II–induced formation of collagen type I in cardiac fibroblasts. Cardiac fibroblasts were treated with different concentrations (10 −8 to 10 −6 M) of Ang II for different times (6 hours, 12 hours, and 24 hours). Ang II increased the expression of collagen type I in a concentration- and time-dependent fashion ( P <0.01 versus control). Ang II also decreased the expression and activity of matrix metalloproteinase (MMP)-1 (MMP-1, P <0.05 versus control). These effects of Ang II were attenuated by pretreatment of cells with pioglitazone (10 μmol/L). Ang II stimulated the intracellular generation of reactive oxygen species (ROS), and this effect was also attenuated by pioglitazone. Ang II treatment activated the redox-sensitive transcription factor NF-κB, and pioglitazone pretreatment blocked this effect of Ang II. Ang II also activated another transcription factor, AP-1, but this effect of Ang II was not modulated by pioglitazone. In other experiments, we observed that trolox, the water soluble analog of vitamin E, attenuated the effects of Ang II on the expression of collagen type I and MMP-1, in a manner similar to pioglitazone. Thus, pioglitazone attenuates Ang II-mediated collagen type I synthesis in cardiac fibroblasts. The effects of pioglitazone are mediated by the modulation of ROS release and redox-sensitive transcription factor NF-κB.

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Hypertension

Tập 44 Số 5

655-661

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