Aggravated Atherosclerosis and Vascular Inflammation With Reduced Kidney Function Depend on Interleukin-17 Receptor A and Are Normalized by Inhibition of Interleukin-17A

Johannes Nordlohne; Alexandra Helmke; Shuwang Ge; Song Rong; Rongjun Chen; Ari Waisman; Hermann Haller; Sibylle von Vietinghoff

doi:10.1016/j.jacbts.2017.08.005

Aggravated Atherosclerosis and Vascular Inflammation With Reduced Kidney Function Depend on Interleukin-17 Receptor A and Are Normalized by Inhibition of Interleukin-17A

JACC Basic Transl Sci. 2018 Jan 10;3(1):54-66. doi: 10.1016/j.jacbts.2017.08.005. eCollection 2018 Feb.

Authors

Johannes Nordlohne¹, Alexandra Helmke¹, Shuwang Ge^{1

2}, Song Rong¹, Rongjun Chen¹, Ari Waisman³, Hermann Haller¹, Sibylle von Vietinghoff¹

Affiliations

¹ Department of Internal Medicine, Division of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.
² Department of Nephrology, Tongji Hospital, Huazhong University of Science and Technology, Huazhong, People's Republic of China.
³ Institute for Molecular Medicine, University of Mainz, Mainz, Germany.

Abstract

Effective therapy of atherosclerotic complications in patients with chronic kidney disease (CKD) is an unmet clinical need. Cardiovascular events are the most common cause of death. At a glomerular filtration rate ≤60 ml/min, these events are increased also after correction for common risk factors. Previous studies have reported enhanced vascular inflammation in mice and recently also in humans. Our current data show, in a mouse model of atherosclerosis in moderate renal impairment, that interleukin-17 receptor A is instrumental in this condition, and blockade of this pathway can normalize arterial inflammation even in advanced atherosclerosis.

Keywords: CKD, chronic kidney disease; IL, interleukin; Il17ra, interleukin-17 receptor A (gene name); LDLr, low-density lipoprotein receptor; PCR, polymerase chain reaction; atherosclerosis; chronic kidney disease; interleukin 17; macrophage.