Obesity-induced vascular inflammation involves elevated arginase activity

Lin Yao, Anil Bhatta, Zhimin Xu, Jijun Chen, Haroldo Alfredo Flores Toque, Yongjun Chen, Yimin Xu, Zsolt Bagi, Rudolf Lucas, Yuqing Huo, Ruth B Caldwell, Robert William Caldwell

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5 Citations (Scopus)

Abstract

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 obesityrelated VAT remodeling and inflammation. Our studies utilized wildtype and EC-A1 knockout (KO) mice made obese by high-fat/highsucrose (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-α (TNF-α), 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 µM) reduced nitric oxide production and increased A1, TNF-α, 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.

Original languageEnglish (US)
Pages (from-to)R560-R571
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume313
Issue number5
DOIs
StatePublished - Nov 1 2017

Fingerprint

Arginase
Blood Vessels
Intra-Abdominal Fat
Obesity
Inflammation
Endothelial Cells
High Fat Diet
Vascular Cell Adhesion Molecule-1
Chemokine CCL2
Intercellular Adhesion Molecule-1
Monocytes
Tumor Necrosis Factor-alpha
Fats
Macrophages
Tissue Expansion
Messenger RNA
Palmitates
Adipocytes
Knockout Mice
Hyperglycemia

Keywords

  • Arginase
  • Endothelial cell activation
  • Inflammation
  • Macrophage
  • Obesity

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

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title = "Obesity-induced vascular inflammation involves elevated arginase activity",
abstract = "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 obesityrelated VAT remodeling and inflammation. Our studies utilized wildtype and EC-A1 knockout (KO) mice made obese by high-fat/highsucrose (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-α (TNF-α), 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 µM) reduced nitric oxide production and increased A1, TNF-α, 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.",
keywords = "Arginase, Endothelial cell activation, Inflammation, Macrophage, Obesity",
author = "Lin Yao and Anil Bhatta and Zhimin Xu and Jijun Chen and {Flores Toque}, {Haroldo Alfredo} and Yongjun Chen and Yimin Xu and Zsolt Bagi and Rudolf Lucas and Yuqing Huo and Caldwell, {Ruth B} and Caldwell, {Robert William}",
year = "2017",
month = "11",
day = "1",
doi = "10.1152/ajpregu.00529.2016",
language = "English (US)",
volume = "313",
pages = "R560--R571",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
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T1 - Obesity-induced vascular inflammation involves elevated arginase activity

AU - Yao, Lin

AU - Bhatta, Anil

AU - Xu, Zhimin

AU - Chen, Jijun

AU - Flores Toque, Haroldo Alfredo

AU - Chen, Yongjun

AU - Xu, Yimin

AU - Bagi, Zsolt

AU - Lucas, Rudolf

AU - Huo, Yuqing

AU - Caldwell, Ruth B

AU - Caldwell, Robert William

PY - 2017/11/1

Y1 - 2017/11/1

N2 - 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 obesityrelated VAT remodeling and inflammation. Our studies utilized wildtype and EC-A1 knockout (KO) mice made obese by high-fat/highsucrose (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-α (TNF-α), 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 µM) reduced nitric oxide production and increased A1, TNF-α, 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.

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 obesityrelated VAT remodeling and inflammation. Our studies utilized wildtype and EC-A1 knockout (KO) mice made obese by high-fat/highsucrose (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-α (TNF-α), 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 µM) reduced nitric oxide production and increased A1, TNF-α, 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.

KW - Arginase

KW - Endothelial cell activation

KW - Inflammation

KW - Macrophage

KW - Obesity

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