Cellular repressor of E1A-stimulated genes (CREG) is a recently discovered secreted glycoprotein involved in homeostatic modulation. We previously reported that CREG is abundantly expressed in the adult vascular endothelium and dramatically downregulated in atherosclerotic lesions. In addition, CREG participates in the regulation of apoptosis, inflammation and wound healing of vascular endothelial cells. In the present study, we attempted to investigate the effect of CREG on the proliferation of vascular endothelial cells and to decipher the underlying molecular mechanisms. Overexpression of CREG in human umbilical vein endothelial cells (HUVEC) was obtained by infection with adenovirus carrying CREG. HUVEC proliferation was investigated by flow cytometry and 5-bromo-2'-deoxy-uridine (BrdU) incorporation assays. The expressions of cyclins, cyclin-dependent kinases and signaling molecules were also examined. In CREG-overexpressing cells, we observed a marked increase in the proportion of the S and G2 population and a decrease in the G0/G1 phase population. The number of BrdU positively-stained cells also increased, obviously. Furthermore, silencing of CREG expression by specific short hairpin RNA effectively inhibited the proliferation of human umbilical vein endothelial cells (HUVEC). CREG overexpression induced the expression of cyclin E in both protein and mRNA levels to regulate cell cycle progression. Further investigation using inhibitor blocking analysis identified that ERK activation mediated the CREG modulation of the proliferation and cyclin E expression in HUVEC. In addition, blocking vascular endothelial growth factor (VEGF) in CREG-overexpressed HUVEC and supplementation of VEGF in CREG knocked-down HUVEC identified that the pro-proliferative effect of CREG was partially mediated by VEGF-induced ERK/cyclin E activation. These results suggest a novel role of CREG to promote HUVEC proliferation through the ERK/cyclin E signaling pathway.

Metabolic disorders are public health problems that require prevention and new efficient drugs for treatment. Cellular repressor of E1A-stimulated genes (CREG) is ubiquitously expressed in mature tissues and cells in mammals and plays a critical role in keeping cells or tissues in a mature, homeostatic state. Recently, CREG turns to be an important mediator in the development of metabolic disorders. Here in this review, we briefly discuss the structure and molecular regulation of CREG along with the therapeutic strategy to combat the metabolic disorders.

Background: The superiority of optical coherence tomography (OCT) guidance over coronary angiography (CA) guidance in optimizing therapy in patients undergoing percutaneous coronary intervention (PCI) remains uncertain. Consequently, we conducted a comprehensive meta-analysis with the objective of providing a higher level of evidence. Methods: The databases of PubMed/Medline, Embase, and Cochrane Central were searched in March 2024. The outcomes of this meta-analysis included all-cause death, cardiovascular death, major adverse cardiovascular events (MACE), restenosis, myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), post-intervention minimum stent area (MSA), post-intervention minimum lumen diameter (MLD), and follow-up MLD. Statistical analysis was conducted using RevMan 5.3 and STATA version 18. The degree of heterogeneity was evaluated using the I² statistical test. When I² exceeded 50%, heterogeneity was deemed to be substantial, prompting the application of a random effects model; conversely, a fixed effects model was employed. The results were expressed as risk ratio (RR) and mean deviation (MD) with their corresponding 95% confidence interval (CI). Results: A total of 25 articles were included in the study. In terms of clinical outcomes, OCT-guided PCI was associated with a significant reduction in all-cause death (RR =0.62; 95% CI: 0.47–0.83; P=0.001), cardiovascular death (RR =0.47; 95% CI: 0.32–0.69; P<0.0001), and MACE (RR =0.65; 95% CI: 0.54–0.77; P<0.00001). Meanwhile, no statistically significant differences were observed for restenosis (RR =0.91; 95% CI: 0.73–1.13; P=0.38), MI (RR =0.83; 95% CI: 0.69–1.00; P=0.05), TLR (RR =0.86; 95% CI: 0.66–1.10; P=0.23), and TVR (RR =0.82; 95% CI: 0.63–1.07; P=0.15). In terms of surrogate endpoints, OCT-guided PCI was associated with a significant enhancement of MSA (MD =0.30; 95% CI: 0.04–0.56; P=0.03) and MLD at follow-up (MD =0.12; 95% CI: 0.02–0.22; P=0.02). Nevertheless, no significant increase in the post-intervention MLD was observed (MD =0.04; 95% CI: −0.02 to 0.10; P=0.19). Conclusions: Compared with CA, the use of OCT for PCI guidance may be an effective strategy to optimize treatment.