The role of transcription factors in the pathogenesis and therapeutic targeting of vascular diseases

Abstract

Transcription factors (TFs) constitute an essential component of epigenetic regulation. They contribute to the progression of vascular diseases by regulating epigenetic gene expression in several vascular diseases. Recently, numerous regulatory mechanisms related to vascular pathology, ranging from general TFs that are continuously activated to histiocyte-specific TFs that are activated under specific circumstances, have been studied. TFs participate in the progression of vascular-related diseases by epigenetically regulating vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). The Krüppel-like family (KLF) TF family is widely recognized as the foremost regulator of vascular diseases. KLF11 prevents aneurysm progression by inhibiting the apoptosis of VSMCs and enhancing their contractile function. The presence of KLF4, another crucial member, suppresses the progression of atherosclerosis (AS) and pulmonary hypertension by attenuating the formation of VSMCs-derived foam cells, ameliorating endothelial dysfunction, and inducing vasodilatory effects. However, the mechanism underlying the regulation of the progression of vascular-related diseases by TFs has remained elusive. The present study categorized the TFs involved in vascular diseases and their regulatory mechanisms to shed light on the potential pathogenesis of vascular diseases, and provide novel insights into their diagnosis and treatment.

Keywords: apoptosis; inflammation; metabolism; proliferation; stress; transcription factors; vascular diseases.

Figure 1

Schematic representation of the regulation of aneurysm-related TFs. The progression of aneurysms is facilitated by the loss of VSMCs, inflammation response, and stress. While the preservation of systolic function of VSMCs prevents aneurysm progression. The stress response encompasses endoplasmic reticulum stress, ROS generation, and vascular endothelial shear stress. VSMC, vascular smooth muscle cells; ER, endoplasmic reticulum; ROS, reactive oxygen species. Created with BioRender.com.

Figure 2

Schematic representation of the regulation of AS-related TFs. The formation of foam cells, cellular dysfunction, and the initiation of an inflammatory response contribute to the development of AS. While the promotion of lipid metabolism restrains AS progression. VSMCs and macrophages constitute the formation of foam cells. VSMCs dysfunction is manifested by pathological proliferation and the transformation into chondroblast. LDL, low-density lipoprotein; VLDL, very low-density lipoprotein; HDL, high-density lipoprotein; IDL, intermediate density lipoprotein; AS, atherosclerosis. Created with BioRender.com.

Figure 3

Schematic representation of the regulation of PAH-related TFs. The alteration in metabolic pattern, the excessive proliferation of PAECs and PASMCs, as well as the dysfunction of PAECs and PAFs, collectively contribute to pulmonary artery remodeling, which is responsible for the progression PAH. While the vasodilatory effect inhibits vascular remodeling. PAECs, pulmonary artery endothelial cells; PASMCs, pulmonary artery smooth muscle cells; PAFs, pulmonary artery fibroblasts. Created with BioRender.com.

Figure 4

Schematic representation of the regulation of Vasculitis-related TFs. The involvement of TFs in T cell activation and differentiation, neutrophil activation and recruitment, as well as exosome-mediated biological processes, play crucial roles in the regulation of vascular wall inflammation. ANCA, anti-neutrophil cytoplasmic antibodies; Th, helper T cell; Tc, cytotoxic T cell; Tfh, follicular helper T cell; Teff, effector T cell; Treg, regulatory T cell. Created with BioRender.com.