PMID- 28835451 OWN - NLM STAT- MEDLINE DCOM- 20171128 LR - 20230813 IS - 1522-1490 (Electronic) IS - 0363-6119 (Print) IS - 0363-6119 (Linking) VI - 313 IP - 5 DP - 2017 Nov 1 TI - Obesity-induced vascular inflammation involves elevated arginase activity. PG - R560-R571 LID - 10.1152/ajpregu.00529.2016 [doi] AB - Obesity-induced vascular dysfunction involves pathological remodeling of the visceral adipose tissue (VAT) and increased inflammation. Our previous studies showed that arginase 1 (A1) in endothelial cells (ECs) is critically involved in obesity-induced vascular dysfunction. We tested the hypothesis that EC-A1 activity also drives obesity-related VAT remodeling and inflammation. Our studies utilized wild-type and EC-A1 knockout (KO) mice made obese by high-fat/high-sucrose (HFHS) diet. HFHS diet induced increases in body weight, fasting blood glucose, and VAT expansion. This was accompanied by increased arginase activity and A1 expression in vascular ECs and increased expression of tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), interleukin-10 (IL-10), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) mRNA and protein in both VAT and ECs. HFHS also markedly increased circulating inflammatory monocytes and VAT infiltration by inflammatory macrophages, while reducing reparative macrophages. Additionally, adipocyte size and fibrosis increased and capillary density decreased in VAT. These effects of HFHS, except for weight gain and hyperglycemia, were prevented or reduced in mice lacking EC-A1 or treated with the arginase inhibitor 2-(S)-amino-6-boronohexanoic acid (ABH). In mouse aortic ECs, exposure to high glucose (25 mM) and Na palmitate (200 muM) reduced nitric oxide production and increased A1, TNF-alpha, VCAM-1, ICAM-1, and MCP-1 mRNA, and monocyte adhesion. Knockout of EC-A1 or ABH prevented these effects. HFHS diet-induced VAT inflammation is mediated by EC-A1 expression/activity. Limiting arginase activity is a possible therapeutic means of controlling obesity-induced vascular and VAT inflammation. FAU - Yao, Lin AU - Yao L AD - School of Pharmaceutical Sciences, South China Research Center for Acupuncture and Moxibustion, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China. AD - Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, Georgia. FAU - Bhatta, Anil AU - Bhatta A AD - Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, Georgia. FAU - Xu, Zhimin AU - Xu Z AD - Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia. FAU - Chen, Jijun AU - Chen J AD - Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, Georgia. FAU - Toque, Haroldo A AU - Toque HA AD - Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, Georgia. FAU - Chen, Yongjun AU - Chen Y AD - South China Research Center for Acupuncture and Moxibustion, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China. FAU - Xu, Yimin AU - Xu Y AD - Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia. FAU - Bagi, Zsolt AU - Bagi Z AD - Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia. AD - Department of Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia. FAU - Lucas, Rudolf AU - Lucas R AD - Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, Georgia. AD - Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia. AD - Department of Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia. FAU - Huo, Yuqing AU - Huo Y AD - Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia. AD - Department of Cell Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia. FAU - Caldwell, Ruth B AU - Caldwell RB AD - Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia. AD - Department of Cell Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia. AD - Veterans Administration Medical Center, Augusta, Georgia; and. FAU - Caldwell, R William AU - Caldwell RW AD - Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, Georgia; wcaldwel@augusta.edu. AD - Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia. LA - eng GR - I01 BX001233/BX/BLRD VA/United States GR - I01 BX003221/BX/BLRD VA/United States GR - R01 DK100564/DK/NIDDK NIH HHS/United States GR - R01 EY011766/EY/NEI NIH HHS/United States PT - Journal Article DEP - 20170823 PL - United States TA - Am J Physiol Regul Integr Comp Physiol JT - American journal of physiology. Regulatory, integrative and comparative physiology JID - 100901230 RN - 0 (Chemokine CCL2) RN - 0 (IL10 protein, mouse) RN - 130068-27-8 (Interleukin-10) RN - EC 3.5.3.1 (Arg1 protein, mouse) RN - EC 3.5.3.1 (Arginase) SB - IM MH - Adipocytes/metabolism/pathology MH - Adipose Tissue/metabolism MH - Animals MH - Arginase/*metabolism MH - Chemokine CCL2/metabolism MH - Inflammation/etiology/metabolism MH - Interleukin-10/metabolism MH - Intra-Abdominal Fat/*metabolism MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Obesity/*complications/metabolism MH - Weight Gain/physiology PMC - PMC5792147 OTO - NOTNLM OT - arginase OT - endothelial cell activation OT - inflammation OT - macrophage OT - obesity EDAT- 2017/08/25 06:00 MHDA- 2017/11/29 06:00 PMCR- 2018/11/01 CRDT- 2017/08/25 06:00 PHST- 2016/12/13 00:00 [received] PHST- 2017/08/08 00:00 [revised] PHST- 2017/08/08 00:00 [accepted] PHST- 2017/08/25 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2017/08/25 06:00 [entrez] PHST- 2018/11/01 00:00 [pmc-release] AID - ajpregu.00529.2016 [pii] AID - R-00529-2016 [pii] AID - 10.1152/ajpregu.00529.2016 [doi] PST - ppublish SO - Am J Physiol Regul Integr Comp Physiol. 2017 Nov 1;313(5):R560-R571. doi: 10.1152/ajpregu.00529.2016. Epub 2017 Aug 23.