TCF7L1 Accelerates Smooth Muscle Cell Phenotypic Switching and Aggravates Abdominal Aortic Aneurysms

Jing Wang; Xiaoxiang Tian; Chenghui Yan; Hanlin Wu; Yuxin Bu; Jia Li; Dan Liu; Yaling Han

doi:10.1016/j.jacbts.2022.07.012

TCF7L1 Accelerates Smooth Muscle Cell Phenotypic Switching and Aggravates Abdominal Aortic Aneurysms

JACC Basic Transl Sci. 2022 Nov 30;8(2):155-170. doi: 10.1016/j.jacbts.2022.07.012. eCollection 2023 Feb.

Authors

Jing Wang¹, Xiaoxiang Tian¹, Chenghui Yan¹, Hanlin Wu¹, Yuxin Bu¹, Jia Li¹, Dan Liu¹, Yaling Han¹

Affiliation

¹ Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China.

Abstract

Phenotypic switching of vascular smooth muscle cells is a central process in abdominal aortic aneurysm (AAA) pathology. We found that knockdown TCF7L1 (transcription factor 7-like 1), a member of the TCF/LEF (T cell factor/lymphoid enhancer factor) family of transcription factors, inhibits vascular smooth muscle cell differentiation. This study hints at potential interventions to maintain a normal, differentiated smooth muscle cell state, thereby eliminating the pathogenesis of AAA. In addition, our study provides insights into the potential use of TCF7L1 as a biomarker for AAA.

Keywords: AAA, abdominal aortic aneurysm; AAV, adeno-associated virus; Ang II, angiotensin II; CVF, collagen volume fraction; MMP, matrix metalloproteinase; PBS, phosphate-buffered saline; PCR, polymerase chain reaction; SM22α, smooth muscle protein 22-α; SMA, smooth muscle actin; SRF, serum response factor; TCF7L1; TCF7L1, transcription factor 7-like 1; VSMC, vascular smooth muscle cell; abdominal aortic aneurysms; cDNA, complementary DNA; mRNA, messenger RNA; phenotypic switching; siRNA, small interfering RNA; smooth muscle cell.