LKB1 delays atherosclerosis by inhibiting phenotypic transformation of vascular smooth muscle cells.

Abstract

BACKGROUND AND OBJECTIVE:

Although liver kinase B1 (LKB1) is a well-known tumor suppressor gene, and its encoded protein has important biological functions, it is not clear whether LKB1 can inhibit atherosclerosis by regulating vascular smooth muscle cells (VSMCs). The purpose of this study is to explore the relationship among LKB1, VSMCs and atherosclerosis.

METHODS AND RESULTS:

ApoE-/- mice with VSMCs-specific overexpression of LKB1 were constructed by adeno-associated virus transfection technique, and then fed with high-fat diet for eight weeks. The effect of LKB1 overexpression on atherosclerosis in mice was investigated by oil red O staining, HE staining, immunofluorescence and Western Blot. The results showed that the expression of LKB1 mRNA and protein in arterial tissue of mice increased significantly after overexpression of LKB1. The degree of atherosclerosis, smooth muscle fiber proliferation and lipid accumulation were significantly alleviated in the overexpression group. The results of Western Blot showed that the expression of α-SMA was increased, while the expression of OPN and CD68 was significantly decreased in the overexpression group (P < 0.05). The Immunofluorescence results of Image Pro Plus software analysis showed that the co-localization relationship between α-SMA and CD68 was more obvious in the control group (P < 0.01).

CONCLUSION:

Our results suggested that LKB1 can delay the progression of atherosclerosis by inhibiting the phenotypic transition of VSMCs.

• Authors: Kaicong Chen, Zhiwen Deng, Chunyan Zhu, Qing Zhang, Rong Chen, Tudi Li, Junqian Luo, Zihao Zhou, Rui Zeng, Tong Zhang, Zhihuan Zeng
• Journal: International journal of cardiology (Int J Cardiol) Vol. 394 Pg. 131363 (Jan 01 2024) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 37722454 (Publication Type: Journal Article)
• Copyright: Copyright © 2023. Published by Elsevier B.V.

Chemical References

• Protein Serine-Threonine Kinases
• RNA, Messenger

Topics

• Mice
• Animals
• Muscle, Smooth, Vascular (metabolism)
• Atherosclerosis (genetics, prevention & control, metabolism)
• Protein Serine-Threonine Kinases (genetics, metabolism)
• RNA, Messenger (metabolism)
• Myocytes, Smooth Muscle (metabolism)
• Cells, Cultured
• Cell Proliferation