Activin receptor-like kinase 7 promotes apoptosis of vascular smooth muscle cells via activating Smad2/3 signaling in diabetic atherosclerosis

Shengchuan Cao; Qiuhuan Yuan; Qianqian Dong; Xilong Liu; Weikang Liu; Xiaoxuan Zhai; Chuanxin Zhang; Han Liu; Mengxiong Tang; Shujian Wei; Yuguo Chen

doi:10.3389/fphar.2022.926433

Activin receptor-like kinase 7 promotes apoptosis of vascular smooth muscle cells via activating Smad2/3 signaling in diabetic atherosclerosis

Front Pharmacol. 2022 Aug 17:13:926433. doi: 10.3389/fphar.2022.926433. eCollection 2022.

Authors

Shengchuan Cao^{1

2

3

4}, Qiuhuan Yuan^{1

2

3

4}, Qianqian Dong^{1

2

3

4}, Xilong Liu^{1

2

3

4}, Weikang Liu^{1

2

3

4}, Xiaoxuan Zhai^{1

2

3

4}, Chuanxin Zhang^{1

2

3

4}, Han Liu^{1

2

3

4}, Mengxiong Tang^{1

2

3

4}, Shujian Wei^{1

2

3

4}, Yuguo Chen^{1

2

3

4}

Affiliations

¹ Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, China.
² Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, China.
³ Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Qilu Hospital of Shandong University, Jinan, China.
⁴ The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China.

Abstract

Vascular smooth muscle cells (VSMCs) is a vital accelerator in the late phase of diabetic atherosclerosis, but the underlying mechanism remains unclear. The aim of our study was to investigate whether activin receptor-like kinase 7 (ALK7)-Smad2/3 pathway plays an important role in VSMC apoptosis of diabetic atherosclerosis. It was shown that ALK7 expression was obviously elevated in the aorta of ApoE^-/- mice with type 2 diabetes mellitus. Inhibition of ALK7 expression significantly improved the stability of atherosclerotic plaques and reduced cell apoptosis. Further experiments showed that ALK7 knockdown stabilized atherosclerotic plaques by reducing VSMC apoptosis via activating Smad2/3. Our study uncovered the important role of ALK7-Smad2/3 signaling in VSMCs apoptosis, which might be a potential therapeutic target in diabetic atherosclerosis.

Keywords: Smad2/3; activin receptor-like kinase 7; apoptosis; diabetic atherosclerosis; vascular smooth muscle cells.