Obesity-induced Endothelial Dysfunction is Prevented by Neutrophil Extracellular Trap Inhibition
Autor: | Daniel T. Eitzman, Chiao Guo, Hui Wang, Jintao Wang, Kyle Kleiman, Jessica Venugopal, Qian Wang |
---|---|
Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine medicine.medical_specialty Endothelium Mice Obese lcsh:Medicine Vasodilation Inflammation 030204 cardiovascular system & hematology Diet High-Fat Extracellular Traps Article Mice 03 medical and health sciences 0302 clinical medicine Cathelicidins Internal medicine medicine Animals Obesity Vascular Diseases Endothelial dysfunction lcsh:Science Mesenteric arteries Chemokine CCL2 Multidisciplinary Electrical impedance myography business.industry Monocyte lcsh:R Neutrophil extracellular traps medicine.disease Mesenteric Arteries 3. Good health Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Endocrinology Cardiovascular Diseases lcsh:Q Endothelium Vascular medicine.symptom business Antimicrobial Cationic Peptides |
Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-7 (2018) Scientific Reports |
ISSN: | 2045-2322 |
DOI: | 10.1038/s41598-018-23256-y |
Popis: | Endothelial dysfunction precedes atherosclerosis and may constitute a critical link between obesity-related inflammation and cardiovascular disease. Neutrophil extracellular traps (NETs) have been shown to promote vascular damage in murine models of autoimmune disease and atherosclerosis. The impact of NETs towards endothelial dysfunction associated with obesity is unknown. Using a diet-induced obesity (DIO) mouse model, this study investigated whether the inhibition or degradation of NETs could reduce the endothelial dysfunction observed in DIO mice. Following induction of DIO, there were elevated plasma concentrations of monocyte chemoattractant protein-1 (MCP-1) and impairment of mesenteric arteriolar vasorelaxation in response to acetylcholine as measured by pressure myography. A marker of NET formation, cathelicidin-related antimicrobial peptide (CRAMP), was markedly increased in mesenteric arterial walls of DIO mice compared to mice on standard chow. Prevention of NET formation with Cl-amidine or dissolution of NETs with DNase restored endothelium-dependent vasodilation to the mesenteric arteries of DIO mice. These findings suggest an instrumental role for NETs in obesity-induced endothelial dysfunction. |
Databáze: | OpenAIRE |
Externí odkaz: |