Contrasting Roles of E2F2 and E2F3 in Cardiac Neovascularization

Abstract

Insufficient neovascularization, characterized by poor endothelial cell (EC) growth, contributes to the pathogenesis of ischemic heart disease and limits cardiac tissue preservation and regeneration. The E2F family of transcription factors are critical regulators of the genes responsible for cell-cycle progression and growth; however, the specific roles of individual E2Fs in ECs are not well understood. Here we investigated the roles of E2F2 and E2F3 in EC growth, angiogenesis, and their functional impact on myocardial infarction (MI). An endothelial-specific E2F3-deficient mouse strain VE-Cre; E2F3fl/fl was generated, and MI was surgically induced in VE-Cre; E2F3fl/fl and E2F2-null (E2F2 KO) mice and their wild-type (WT) littermates, VE-Cre; E2F3+/+ and E2F2 WT, respectively. The cardiac function, infarct size, and vascular density were significantly better in E2F2 KO mice and significantly worse in VE-Cre; E2F3fl/fl mice than in their WT littermates. The loss of E2F2 expression was associated with an increase in the proliferation of ECs both in vivo and in vitro, while the loss of E2F3 expression led to declines in EC proliferation. Thus, E2F3 promotes while E2F2 suppresses ischemic cardiac repair through corresponding changes in EC proliferation; and differential targeting of specific E2F members may provide a novel strategy for therapeutic angiogenesis of ischemic heart disease.

ERBB2 Deficiency Alters an E2F-1-Dependent Adaptive Stress Response and Leads to Cardiac Dysfunction

“…4C; also see Table S10 in the supplemental material). E2F-1 but not other E2F family members (E2F-2, E2F-3, and E2F-7) known to play a role in cardiac development and function (20)(21)(22) was markedly decreased in ERBB2 KI hearts compared to WT hearts (Fig. 4D).…”

Glomerulocapillary miRNA response to HLA-class I antibody in vitro and in vivo

“…Upregulation of miR-195-5p seems to have equivocal effects. It suppresses proangiogenic target E2F3 34 , 35 . Another target, endothelial CDC42, inhibits various mechanisms of blood vessel formation 36 – 39 .…”

GRB10 and E2F3 as Diagnostic Markers of Osteoarthritis and Their Correlation with Immune Infiltration

“…Inhibition of E2F3 expression promotes the development of diabetic nephropathy [35]. Furthermore, E2F3 plays a key role in various biological processes such as lens development, cardiac neovascularization, DNA damage response, and neuronal migration [36][37][38][39]. E2F3 protein is an important participant in the cell cycle process, and an abnormal regulation of the cell cycle is closely related to the development of OA [40].…”