Abstract
Proliferation and oxidative stress of vascular smooth muscle cells (VSMCs) contribute to vascular remodeling in hypertension and several major vascular diseases. B-cell lymphoma 6 (BCL6) functions as a transcriptional repressor. The present study is designed to determine the roles of BCL6 in VSMC proliferation and oxidative stress and underlying mechanism. Angiotensin (Ang) II was used to induce VSMC proliferation and oxidative stress in human VSMCs. Effects of BCL6 overexpression and knockdown were, respectively, investigated in Ang II-treated human VSMCs. Therapeutical effects of BCL6 overexpression on vascular remodeling, oxidative stress, and proliferation were determined in the aorta of spontaneously hypertensive rats (SHR). Ang II reduced BCL6 expression in human VSMCs. BCL6 overexpression attenuated while BCL6 knockdown enhanced the Ang II-induced upregulation of NADPH oxidase 4 (NOX4), production of reactive oxygen species (ROS), and proliferation of VSMCs. BCL6 expression was downregulated in SHR. BCL6 overexpression in SHR reduced NOX4 expression, ROS production, and proliferation of the aortic media of SHR. Moreover, BCL6 overexpression attenuated vascular remodeling and hypertension in SHR. However, BCL6 overexpression had no significant effects on NOX2 expression in human VSMCs or in SHR. We conclude that BCL6 attenuates proliferation and oxidative stress of VSMCs in hypertension.
Highlights
Vascular smooth muscle cells (VSMCs) are dominant cellular constituent of arteries [1, 2]
Primary novel findings in the present study are that B-cell lymphoma 6 (BCL6) inhibits Angiotensin II (Ang II)-induced oxidative stress and proliferation in human VSMCs, and BCL6 overexpression attenuates oxidative stress and vascular remodeling in the aorta of spontaneously hypertensive rats (SHR)
It is well known that Ang II induces VSMC proliferation [27], which is widely used as a model of VSMC proliferation in vitro [28,29,30]
Summary
Vascular smooth muscle cells (VSMCs) are dominant cellular constituent of arteries [1, 2]. VSMC proliferation is closely linked with vascular remodeling and stiffening in the initiation and progression of vascular diseases such as hypertension, atherosclerosis, myocardial hypertrophy, myocardial infarction, stroke, dementia, and renal failure [3,4,5]. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is a major source of reactive oxygen species (ROS) in VSMCs and is essential to cell proliferation [6]. It is known that Ang II binds to Ang II type 1 receptor (AT1R) and activates NOX and promotes ROS generation and VSMC proliferation [7,8,9]. Intervention of reninangiotensin system in hypertensive patients lowers morbidity and mortality [13, 14]
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