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Published on: January 4, 2018
Angiotensin receptor-binding molecule in leukocytes in association with the systemic and leukocyte inflammatory
Kotaro Haruhara1, Hiromichi Wakui2, Kengo Azushima3
1Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan; Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Insights
Leukocyte Angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP) mRNA is abundant in healthy individuals and correlates with inflammation markers in non-communicable diseases (NCDs). ATRAP may act as an anti-inflammatory factor in NCDs.
Area of Science:
- Immunology
- Cardiovascular Science
- Nephrology
Background:
- The renin-angiotensin system in leukocytes contributes to non-communicable diseases (NCDs) like hypertension and atherosclerosis.
- Angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP) inhibits pathological AT1R signaling in animal models.
- Investigating ATRAP expression and regulation in leukocytes is crucial for understanding NCDs.
Purpose of the Study:
- To investigate the expression and regulation of ATRAP in human leukocytes.
- To determine the association between leukocyte ATRAP mRNA levels and clinical variables in NCD patients.
- To explore the role of ATRAP in leukocyte inflammation.
Main Methods:
- Droplet digital polymerase chain reaction (ddPCR) was used to measure human leukocyte ATRAP mRNA.
- Leukocyte ATRAP mRNA levels were analyzed in relation to clinical variables in 86 NCD outpatients.
- Leukocyte cytokine mRNA was examined in bone-marrow ATRAP-deficient and wild-type chimeric mice after lipopolysaccharide injection.
Main Results:
- ATRAP mRNA was highly expressed in leukocytes, particularly granulocytes and monocytes, of healthy subjects.
- Leukocyte ATRAP mRNA levels positively correlated with granulocyte, monocyte counts, and C-reactive protein in NCD patients.
- ATRAP mRNA levels were associated with inflammatory cytokines (IL-1β, TNF-α, MCP-1) in NCD patients' leukocytes. Leukocyte IL-1β was upregulated in ATRAP-deficient mice.
Conclusions:
- Leukocyte ATRAP serves as a marker for systemic and leukocyte inflammation.
- ATRAP appears to function as an anti-inflammatory factor in the pathophysiology of NCDs.
- Further research into ATRAP's role could offer new therapeutic strategies for NCDs.
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-1β, tumor necrosis factor-α and monocyte chemotactic protein-1 mRNA levels in leukocytes of NCDs patients. In addition, the leukocyte interleukin-1β 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.
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