Regulation of angiotensin II-induced B-cell lymphoma-2-associated athanogene 3 expression in vascular smooth muscle cells

Abstract

Previous studies have demonstrated that angiotensin II (Ang II) is involved in the process of atherosclerosis and vascular restenosis through its proinflammatory effect. Bcl‑2‑associated athanogene 3 (BAG3) had been suggested to be associated with proliferation, migration and invasion in many types of tumor. However, the role of BAG3 among the proliferative process of vascular smooth muscle cells (VSMCs) induced by Ang II, to the best of our knowledge, remains to be investigated. The present study demonstrated that in growth‑arrested VSMCs, Ang II‑induced VSMC proliferation, accompanied by increased BAG3 mRNA and protein expression levels in a dose‑ and time‑dependent manner. BAG3 expression levels were measured in VSMCs treated in the presence or absence of Ang II. The proliferation of VSMCs was assessed using manual cell counting and Cell Counting kit‑8 assays. mRNA and protein expression levels of BAG3, Toll‑like receptor 4 (TLR4), proliferating cell nuclear antigen, nuclear factor (NF)‑κB p65, smooth muscle protein 22α and phosphorylated NF‑κB p65 were assessed by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. In non‑transfected or scramble short hairpin RNA (shRNA)‑transfected VSMCs cells, Ang II significantly induced VSMC proliferation. However, this Ang II‑induce proliferation was attenuated when BAG3 was silenced, suggesting that inhibition of BAG3 may somehow reduce proliferation in Ang II‑induced VSMCs. Furthermore, the TLR4/NF‑κB p65 signaling pathway was involved in BAG3 gene upregulation. In conclusion, to the best of our knowledge, the present study demonstrated for the first time that inhibition of BAG3 attenuates cell proliferation. Furthermore, Ang II induced VSMCs proliferation through regulation of BAG3 expression via the TLR4/NF‑κB p65 signaling pathway.

Keywords: Bcl-2 associated athanogene 3; angiotensin II; vascular smooth muscle cells; proliferation.