Title:Luteolin Antagonizes Angiotensin II-Dependent Proliferation and Collagen Synthesis of Cultured rat Cardiac Fibroblasts
Volume: 16
Issue: 5
Author(s): Tingting Wang, Defeng Pan, Yingying Zhang, Dongye Li, Yanbin Zhang, Tongda Xu, Yuanyuan Luo and Yanfeng Ma
Affiliation:
Keywords:
Angiotensin II, cardiac fibroblast, cGMP, fibrosis, luteolin, nitric oxide.
Abstract: Objective: The purpose of this study was to observe if luteolin could affect the behavior
of cardiac fibroblasts (CFs) on myocardial fibrosis stimulated by angiotensin II (Ang II) and investigate
the mechanism involved. Methods: MTT was used to observe the CFs viability and proliferation
which was also detected by an EdU staining kit. Cell migration was determined by the transwell
chamber. Western blotting was used to examine the protein expression levels of a smooth muscle actin (α -SMA),
collagen I and collagen III. The activity of nitric oxide (NO), synthase (NOS), nitrite and cyclic GMP (cGMP) content
were measured according to the kits and an enzyme linked immunosorbent assay (ELISA) respectively. Results: The proliferation,
migration and expression of α-SMA, collagen I and collagen III in CFs stimulated by Ang II were inhibited by
luteolin treatment, and these effects were partly blocked by a combination of treatment with Ang II and NG-nitro-Larginine
methyl ester (L-NAME), a non-selective NOS inhibitor, also with 1H-[1,2,4]-oxadiazole -[4,3-a]-quinoxalin-1-
one (ODQ), a specific inhibitor of guanylyl cyclase. These effects did not include CFs migration, which showed no apparent
difference between Ang II single and together with inhibitors. Luteolin increased the synthesis of total NOS and the
content of nitrite and cGMP. Conclusion: These results demonstrate that luteolin is capable of inhibiting the behavior of
CFs stimulated by Ang II via up-regulation of NO-cGMP signal pathway.
