ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SA-PO1078

Leukocyte Angiotensin II Type 1 Receptor-Associated Protein as a Surrogate Marker and Inhibitory Factor of Inflammation

Session Information

Category: Hypertension

  • 1101 Hypertension: Basic and Experimental - Neural and Inflammatory Mechanisms

Authors

  • Haruhara, Kotaro, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • Wakui, Hiromichi, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • Kobayashi, Ryu, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • Kurotaki, Daisuke, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • Tsuboi, Nobuo, The Jikei University School of Medicine, Tokyo, Japan
  • Yokoo, Takashi, The Jikei University School of Medicine, Tokyo, Japan
  • Tamura, Kouichi, Yokohama City University Graduate School of Medicine, Yokohama, Japan
Background

Previous studies have shown that the leukocyte gene expression of the renin-angiotensin system, particularly type1 angiotensin II receptor (AT1R), is involved in the pathogenesis of non-communicable diseases (NCD) and its target organ diseases. We found that AT1R-associated protein (ATRAP) is a novel molecule that specifically binds to AT1R and promotes internalization of AT1R along with the suppression of activated AT1R signal in animal models of NCD. The aim of this study was to determine the factors that may regulate the gene expression of ATRAP in leukocytes.

Methods

Blood samples were obtained from healthy volunteers and NCD patients. We examined the relationships between leukocyte ATRAP mRNA and clinical variables. Bone marrow ATRAP-deficient chimeric mice and bone marrow wild-type mice as control were generated by a procedure of bone marrow transplantation. After injection of low-dose lipopolysaccharide, these mice were sacrificed and measured inflammatory cytokines mRNA expression in leukocytes.

Results

ATRAP was expressed predominantly in granulocytes and monocytes from healthy volunteers. In blood samples from 86 patients (mean age 63 years, hypertension in 95%, dyslipidemia in 76%, chronic kidney disease in 63%), the ATRAP mRNA was positively correlated with the age, neutrophil count, monocyte count, and serum CRP. These associations remained significant after adjustment for age, sex, estimated glomerular filtration rate, and urinary albumin excretion. Furthermore, the ATRAP mRNA was positively correlated with the IL-1β, TNF-α and MCP-1 mRNA in leukocytes. In addition, these cytokines were upregulated in bone marrow ATRAP-deficient chimeric mice in comparison to control mice after injection of low-dose lipopolysaccharide.

Conclusion

These results suggest that leukocyte ATRAP expression is associated with systemic and leukocyte inflammatory status and increases to compensate for inflammation.