OBJECTIVE: Atrial fibrillation (AF) has been identified to contribute significantly to the morbidity and mortality of cardiovascular disease patients. The atrial structural remodeling is a hallmark of AF and the molecular mechanisms underlying this remain unclear. Hence the objective of the present study is to determine the role of angiotensin II (Ang-II)/Ang-II type 1 (AT1) receptor – STAT3 signaling pathway on – atrial structural remodeling.
MATERIALS AND METHODS: The method of this study involves incubation of atrial myocytes, with Ang-II, to increase the level of apoptosis expressions by Tunel assay and the expression of apoptosis related factors like caspase 3 and 8 release of cytochrome C from mitochondria to cytosol by western blot test after OGD pre-treatment.
RESULTS: Atrial myocytes were shown to simulate the ischemia, hypoxia and atrial fibrillation. When incubated with Ang-II, (inhibited by losartan) the improvement was observed in the expression of caspase-3 and caspase-8. Ang-II also significantly promoted the transfer of cytochrome C levels from the mitochondria to the cytoplasm and this transfer was observed to be inhibited by losartan and WP1066. Ang-II incubation showed improved transcriptions of collagens and MMP expressions in atrial fibroblasts. In cultured atrial myocytes and fibroblasts, Ang-II induced tyrosine and serine phosphorylation of STAT3 showing interaction with MMP1 and MMP2 and DNA promoter sequences in atrial fibroblasts. The complete sequence was observed to have an affinity to be inhibited by losartan and WP1066.
CONCLUSIONS: Ang-II/AT1 receptor/STAT3 is an important signaling pathway in the atrial structural remodeling, Ang-II enhances the apoptosis of atrial parenchyma and deposition of atrial ECM, which might contributes to atrial fibrillation.Free PDF Download
To cite this article
L.-Y. Zheng, M.-H. Zhang, J.-H. Xue, Y. Li, Y. Nan, M.-J. Li, J. Wang, X.-P. Du
Effect of Angiotensin II on STAT3 mediated atrial structural remodeling
Eur Rev Med Pharmacol Sci
Vol. 18 - N. 16