期刊
ATHEROSCLEROSIS
卷 269, 期 -, 页码 236-244出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2018.01.013
关键词
Inflammation; Leukocyte; Non-communicable diseases; Receptor; Renin-angiotensin system
资金
- Jikei University Graduate Research Fund
- Yokohama Foundation for advancement of Medical Science
- Uehara Memorial Foundation
- Japan Society for the Promotion of Science
- SENSHIN Medical Research
- Banyu Life Science Foundation International
- Salt Science Research Foundation [1733]
- Kanae Foundation for the Promotion of Medical Science
- Cardiovascular Research Fund, Tokyo, Japan
- Grants-in-Aid for Scientific Research [17K19665] Funding Source: KAKEN
Background and aims: The components of the renin-angiotensin system in leukocytes is involved in the pathophysiology of non-communicable diseases (NCDs), including hypertension, atherosclerosis and chronic kidney disease. Angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP) is an AT1R-specific binding protein, and is able to inhibit the pathological activation of AT1R signaling in certain animal models of NCDs. The aim of the present study was to investigate the expression and regulation of ATRAP in leukocytes. Methods: Human leukocyte ATRAP mRNA was measured with droplet digital polymerase chain reaction system, and analyzed in relation to the clinical variables. We also examined the leukocyte cytokines mRNA in bone-marrow ATRAP-deficient and wild-type chimeric mice after injection of low-dose lipopolysaccharide. Results: The ATRAP mRNA was abundantly expressed in leukocytes, predominantly granulocytes and monocytes, of healthy subjects. In 86 outpatients with NCDs, leukocyte ATRAP mRNA levels correlated positively with granulocyte and monocyte counts and serum C-reactive protein levels. These positive relationships remained significant even after adjustment. Furthermore, the leukocyte ATRAP mRNA was significantly associated with the interleukin-1 beta, tumor necrosis factor-a and monocyte chemotactic protein-1 mRNA levels in leukocytes of NCDs patients. In addition, the leukocyte interleukin-1 beta mRNA level was significantly upregulated in bone marrow ATRAP-deficient chimeric mice in comparison to wild-type chimeric mice after injection of lipopolysaccharide. Conclusions: These results suggest that leukocyte ATRAP is an emerging marker capable of reflecting the systemic and leukocyte inflammatory profile, and plays a role as an anti-inflammatory factor in the pathophysiology of NCDs. (C) 2018 Elsevier B.V. All rights reserved.
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