ADVANCED GLYCATION END PRODUCTS(AGES) AND DIETARY METABOLITES RESULTED IN NEUTROPHIL EXTRACELLULAR TRAPS (NETS) AND VASCULAR CHRONIC INFLAMMATION AND STIFFNESS

Abstract

Inflammaging is a risk factor for cardiovascular diseases. Advanced glycation end products (AGEs) are proteins or lipids that become glycated as a result of exposure to sugars, they are thought to be a detrimental metabolite involving in inflammation and some age-related chronic diseases. To explore the effects of vascular aging via the immune pathway.To investigate the role of AGEs in inducing neutrophil activation and cause neutrophil extracellular traps (NET), Neutrophil cell line treated with AGEs analyzed the reactive oxygen species (ROS) production and proinflammatory cytokines expression. Whether AGEs cause the morphological and functional change in endothelial cells by using a human cell line HMEC-1. Next, we investigate if older people bear spontaneous NET in the circulation that may bring detrimental impact in the vasculature system. We enrolled volunteers > 65 years-old, the serum was measured with MPO-DNA complex by ELISA. In vivo, we established an animal model by feeding mice with a high-fat diet (HFD) for long period to induce chronic intestinal inflammation. The aortic stiffness was assessed in vivo by the pulse wave velocity (PWV) after HFD feeding and normal diet (ND) feeding for 20 weeks.AGE not only caused neutrophil cell line cellular ROS generation in time-dependent manners but also significantly increased expression of TNF and il-1, and AGE increased expression of inflammation markers including ICAM-1, VCAM-1, DLC-1 and reduced tube formation by HMEC-1. AGEs induced the NETs formation in primary neutrophils in a time-dependent manner. Volunteer serum MPO-DNA complex is higher than younger donors, HFD-feeding mice had increased and PWV and decreased colon of length, compared with ND-feeding mice, suggesting PWV tends to increase with higher arterial stiffness.In conclusion, AGEs, a metabolite from HFD is able to induce neutrophil activation and NET formation. Volunteers > 65 years old have high MPO-DNA complex, suggesting the "Netting" neutrophil in the circulation would be one of the potential factors causing the inflammation in the vessel and leading to vessel stiffness. The HFD-feeding mice with intestinal inflammation display vascular stiffness.