Anti-TNF-α Antibody (Infliximab) Therapy Supports the Recovery of eNOS and VEGFR2 Protein Expression in Endothelial Cells

Abstract

The aim of this study is to investigate the effect of sera obtained from patients of Crohn's disease treated by anti-TNF-alpha antibody (Infliximab) on the expression of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor receptor-2 (VEGFR2) protein in human umbilical vein endothelial cells (HUVEC) cultured in vitro. HUVEC was cultured in the presence of sera derived from patients before and after treatment, or from healthy individuals. Effects of sera on the expression of eNOS and VEGFR2 were monitored by determination of mRNA and protein levels using real time quantitative PCR and Western blot analysis, respectively. The serum of Crohn's patients contained elevated levels of TNF-alpha (34±1.80 pg/mL), which resulted in a decrease in the protein level of eNOS in HUVEC with a simultaneous induction of VEGFR2. Infliximab treatment normalized the expression level of these proteins by decreasing TNF-alpha level, particularly in those cases when clinical healing was also recorded, and it also conferred restitution of the level of angiogenic cytokines. Results suggest that altered angiogenesis possibly contributes to the initiation and perpetuation of inflammatory processes in inflammatory bowel disease (IBD). Endothelial dysfunction, a selective feature of Crohn's disease is beneficially affected by intravascular TNF-alpha neutralization.

Infliximab prevents increased systolic blood pressure and upregulates the AKT/eNOS pathway in the aorta of spontaneously hypertensive rats

“…Importantly, these results obtained by Tesauro et al (2008) demonstrated that the effect of infliximab was dependent on NO synthesis. In addition, sera that were obtained from patients with Crohn's disease who were treated with infliximab induced increased eNOS expression when added to human umbilical vein endothelial cells (Altorjay et al, 2011). Our data also show that infliximab did not alter blood pressure values in normotensive WKY rats.…”

Endothelial Cells, Cholesterol, Cytokines, and Aging

“…Increasing the turnover of bile salts has a beneficial effect on low-density lipoprotein cholesterol levels, which is an important risk factor for the development of atherosclerosis and playa relevant role in aging (24-29). Elevated plasma LDL cholesterol and triglyceride levels and reduced HDL cholesterol levels are associated with an increased risk of developing atheroma and shorter life (30)(31)(32)(33)(34)(35).…”

Anti-angiogenic effects of biotechnological therapies in rheumatic diseases

“…Anti-TNF-α agents have also demonstrated anti-angiogenic effects in chronic inflammatory diseases such as psoriasis and Crohn’s disease. 23 , 24 By using in vitro and in vivo models, Liu et al 25 have proposed a dual mechanism to explain the anti-psoriatic effect of IBI303, an anti-TNF-α monoclonal antibody, based on the inhibition of both inflammation and angiogenesis, with a direct inhibition of the anti-TNF-α agent on blood vessel formation in vitro. Among rheumatic diseases, anti-TNF-α agents have shown anti-angiogenic properties in RA and PsA.…”