Abstract 14859: IL17 Contribute to the Atherosclerotic Development and the Initiation of Chronic Kidney Disease
Introduction: Recent studies suggested that the atherogenic state correlated with progression of chronic kidney disease (CKD). However, it is not known whether sustained status of chronic inflammation in atherosclerosis is closely linked to the development of CKD.
Hypothesis: Inflammatory cytokine producing-T cells in the advanced atherosclerosis induced the dysfunction of podocytes.
Methods/Results: Eighteen-week-old apolipoprotein E-deficient mice (Control) were fed with high-fat diet for 8W (ApoE) and compared to IL17/ApoE-double deficient mice fed with high-fat diet (DKO). Sudan staining of aorta revealed the atherosclerotic lesion was increased in ApoE compared to Control, and inhibited in DKO. Activated IFNγ+ CD4 T cells (Th1) and IL17+ CD4 T cells (Th17) were significantly increased in ApoE compared to DKO by FACS. Immunohistochemistry of aortic sinus showed many Th1 and Th17 were infiltrated in the atherosclerotic plaque in ApoE, however, inflammatory infiltrates were inhibited in DKO. Furthermore, the urinary albumin/creatinine ratio was increased significantly in ApoE compared to DKO. Th1 and Th17 were correlated with the urinary albumin/creatinine ratio, and many Th1 and Th17 were observed in the glomeruli. Next, to investigate whether the inflammatory cytokine induced dysfunction of podocytes were involved in proteinuria, we investigated nephrin, podocin, and phosphorylated nephrin in the kidney by Western blots and immunohistochemistry. The decreased phosphorylated neprin in ApoE were recovered in DKO. Finally, we confirmed that the morphological changed of podocytes in ApoE were improved in DKO by electron microscopy.
Conclusion: Recruitments of IFNγ+ Th1 and IL17+ Th17 T cells might aggravate atherosclerosis acceleration and induce the initiation of glomerular tissue damage.
Author Disclosures: Y. Tanigaito: None. K. Sato: None. K. Kitamura: None. A. Futase: None. K. Fukushima: None. K. Uto: None. N. Hagiwara: None.
- © 2014 by American Heart Association, Inc.