Deletion of the FHL2 gene attenuates intima‐media thickening in a partially ligated carotid artery ligated mouse model

Abstract

The four and a half LIM domain protein 2 (FHL2) is a member of the four and a half LIM domain (FHL) gene family, and it is associated with cholesterol‐enriched diet‐promoted atherosclerosis. However, the effect of FHL2 protein on vascular remodelling in response to hemodynamic alterations remains unclear. Here, we investigated the role of FHL2 in a model of restricted blood flow‐induced atherosclerosis. To promote neointimal hyperplasia in vivo, we subjected FHL2+/+ and FHL2−/− mice to partial ligation of the left carotid artery (LCA). The expression of p‐ERK and p‐AKT was decreased in FHL2−/− mice. FHL2 bound to AKT regulated AKT phosphorylation and led to Rac1‐GTP inactivation. FHL2 silencing in human aortic smooth muscle cells down‐regulated the PDGF‐induced phosphorylation of ERK and AKT. Furthermore, FHL2 silencing reduced cytoskeleton conformational changes and caused cell cycle arrest. We concluded that FHL2 is essential for the regulation of arterial smooth muscle cell function. FHL2 modulates proliferation and migration via mitogen‐activated protein kinase (MAPK) and PI3K‐AKT signalling, leading to arterial wall thickening and thus neointimal hyperplasia.

Integrated transcriptomic and neuroimaging brain model decodes biological mechanisms in aging and Alzheimer’s disease

“…CAST overexpression was shown to reduce amyloid burden due to its effect on BACE1 processing of A PP ( Liang et al, 2010 ; Morales-Corraliza et al, 2012 ). FHL2 prevents inflammatory angiogenesis and regulates the function of vascular smooth muscle cells, suggesting its role in blood flow ( Chen et al, 2020 ; Chu et al, 2008 ). IGF2R (insulin-like growth factor two receptor) interacts with insulin receptors for energy homeostasis, and the dysregulation of the gene is associated with type 2 diabetes ( Chanprasertyothin et al, 2015 ).…”

Integrated Transcriptomic and Neuroimaging Brain Model Decodes Biological Mechanisms in Aging and Alzheimer’s Disease

“…F HL2 prevents inflammatory angiogenesis and regulates the function of vascular smooth muscle cells, suggesting its role in blood flow (C. Y. Chen et al, 2020; Chu et al, 2008). IGF2R (insulin-like growth factor 2 receptor) interacts with insulin receptors for energy homeostasis, and the dysregulation of the gene is associated with type 2 diabetes (Chanprasertyothin et al, 2015).…”

“…FHL2 prevents inflammatory angiogenesis and regulates the function of vascular smooth muscle cells, suggesting its role in blood flow (C. Y. Chen et al, 2020;Chu et al, 2008). IGF2R…”

How (Epi)Genetic Regulation of the LIM-Domain Protein FHL2 Impacts Multifactorial Disease

“…FHL2 is expressed most abundantly in the heart, blood vessels, ovary, and skeletal muscle, and to a lesser extent in several other organs [5][6][7][8]. FHL2 expression and function have been studied in a number of diseases, including various types of cancer [9][10][11][12], cardiovascular disease [5,6,8,[13][14][15], and overall metabolism [16]. At present, information regarding the exact regulation of FHL2 expression is limited [17,18].…”

“…These recent findings suggest a potentially pivotal role for methylation in regulating FHL2 expression and function in age-related disorders. FHL2 is expressed most abundantly in the heart, blood vessels, ovary, and skeletal muscle, and to a lesser extent in several other organs [5][6][7][8]. FHL2 expression and function have been studied in a number of diseases, including various types of cancer [9][10][11][12], cardiovascular disease [5,6,8,[13][14][15], and overall metabolism [16].…”