The Role of the VEGF Family in Coronary Heart Disease

Abstract

The vascular endothelial growth factor (VEGF) family, the regulator of blood and lymphatic vessels, is mostly investigated in the tumor and ophthalmic field. However, the functions it enjoys can also interfere with the development of atherosclerosis (AS) and further diseases like coronary heart disease (CHD). The source, regulating mechanisms including upregulation and downregulation, target cells/tissues, and known functions about VEGF-A, VEGF-B, VEGF-C, and VEGF-D are covered in the review. VEGF-A can regulate angiogenesis, vascular permeability, and inflammation by binding with VEGFR-1 and VEGFR-2. VEGF-B can regulate angiogenesis, redox, and apoptosis by binding with VEGFR-1. VEGF-C can regulate inflammation, lymphangiogenesis, angiogenesis, apoptosis, and fibrogenesis by binding with VEGFR-2 and VEGFR-3. VEGF-D can regulate lymphangiogenesis, angiogenesis, fibrogenesis, and apoptosis by binding with VEGFR-2 and VEGFR-3. These functions present great potential of applying the VEGF family for treating CHD. For instance, angiogenesis can compensate for hypoxia and ischemia by growing novel blood vessels. Lymphangiogenesis can degrade inflammation by providing exits for accumulated inflammatory cytokines. Anti-apoptosis can protect myocardium from impairment after myocardial infarction (MI). Fibrogenesis can promote myocardial fibrosis after MI to benefit cardiac recovery. In addition, all these factors have been confirmed to keep a link with lipid metabolism, the research about which is still in the early stage and exact mechanisms are relatively obscure. Because few reviews have been published about the summarized role of the VEGF family for treating CHD, the aim of this review article is to present an overview of the available evidence supporting it and give hints for further research.

PSMA-bearing extracellular vesicles secreted from prostate cancer convert the microenvironment to a tumor-supporting, pro-angiogenic state

“…These TME modifications are enhanced and altered by time to prime tumor tissue to lymphangiogenesis, that it is sustained by the activation of 4EBP-1 via phosphorylation. Importantly, VEGF can also lead to activation of this pathway (Abid et al, 2004; Zhou et al, 2021).…”

The Angiogenic Balance and Its Implications in Cancer and Cardiovascular Diseases: An Overview

“…The class of VEGF proteins consists of several derivatives such as VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E (encoded-virus) and VEGF-F (derived from snake venom) and placental growth factor (PlGF) [ 5 , 7 , 8 ]. Vascular permeability and inflammation, angiogenesis and apoptosis, lymphangio-genesis and fibrogenesis can be adjusted by the VEGF family [ 8 ].…”

“…The class of VEGF proteins consists of several derivatives such as VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E (encoded-virus) and VEGF-F (derived from snake venom) and placental growth factor (PlGF) [ 5 , 7 , 8 ]. Vascular permeability and inflammation, angiogenesis and apoptosis, lymphangio-genesis and fibrogenesis can be adjusted by the VEGF family [ 8 ]. From all the VEGF class components, VEGF-A is the most individualized, representing a substantial angiogenesis promotor and consequently designed as an objective for the study of certain anti-cancer therapies [ 7 , 9 ].…”

“…From all the VEGF class components, VEGF-A is the most individualized, representing a substantial angiogenesis promotor and consequently designed as an objective for the study of certain anti-cancer therapies [ 7 , 9 ]. According to the chain length, different VEGF-A isoforms have resulted after the splicing of alternative VEGF mRNA [ 8 ], and have further been referred to as VEGF XXX , where “XXX” indicates the number of amino acids from the final protein chain [ 7 ]. The most well-known subtypes are VEGF 111 , VEGF 121 , VEGF 145 , VEGF 165 , VEGF 189 and VEGF 206 [ 5 ].…”

“…The vascular endothelial growth factor (VEGF) action is closely related to the stimulation of angiogenesis [ 5 , 6 ]. The VEGF proteins family consists of six members [ 5 , 7 , 8 ], with VEGF-A being the most studied, included in certain anti-cancer therapies [ 7 , 9 ]. Exogenous compounds such as polypeptides [ 10 ] or small synthetic molecules, antibiotics, saccharides and steroids have been shown to induce angiogenesis regulation [ 11 , 12 ].…”