Pioglitazone attenuated Angiotensin II-mediated collagen type I synthesis in cardiac fibroblasts by modulating reactive oxygen species release and NF-kappaB activation.
Does pioglitazone reduce Angiotensin II-induced collagen type I synthesis in cardiac fibroblasts?
Pioglitazone attenuates Angiotensin II-mediated collagen type I synthesis in cardiac fibroblasts by modulating reactive oxygen species release and NF-kappaB activation, suggesting a potential mechanism to reduce cardiac remodeling.
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-gamma 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 micromol/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-kappaB, 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-kappaB.
Chen et al. (Tue,) reported a other. Pioglitazone vs. Control (Angiotensin II alone) was evaluated on Expression of collagen type I. Pioglitazone attenuated Angiotensin II-mediated collagen type I synthesis in cardiac fibroblasts by modulating reactive oxygen species release and NF-kappaB activation.