HIV-associated nephropathy: role of AT2R |
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| Authors: | Salhan Divya Sagar Ankita Kumar Dileep Rattanavich Rungwasee Rai Partab Maheshwari Subani Adabala Madhuri Husain Mohammad Ding Guohua Malhotra Ashwani Chander Praveen N Singhal Pravin C |
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| Institution: | Division of Kidney Diseases and Hypertension, North Shore-LIJ Health System, Great Neck, NY, United States Department of Pathology, New York Medical College, Valhalla, NY, United States |
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| Abstract: | AT1R has been reported to play an important role in the progression of HIV-associated nephropathy (HIVAN); however, the effect of AT2R has not been studied. Age and sex matched control (FVB/N) and Tg26 mice aged 4, 8, and 16 weeks were studied for renal tissue expression of AT1R and AT2R (Protocol A). Renal tissue mRNA expression of AT2R was lower in Tg26 mice when compared with control mice. In Protocol B, Tg26 mice were treated with either saline, telmisartan (TEL, AT1 blocker), PD123319 (PD, AT2R blocker), or TEL + PD for two weeks. TEL-receiving Tg26 (TRTg) displayed less advanced glomerular and tubular lesions when compared with saline-receiving Tg26 (SRTg). TRTgs displayed enhanced renal tissue AT2R expression when compared to SRTgs. Diminution of renal tissue AT2R expression was associated with advanced renal lesions in SRTgs; whereas, upregulation of AT2R expression in TRTgs was associated with attenuated renal lesions. PD-receiving Tg26 mice (PDRTg) did not show any alteration in the course of HIVAN; whereas, PD + TEL-receiving Tg26 (PD-TRTg) showed worsening of renal lesions when compared to TRTgs. Interestingly, plasma as well as renal tissues of Tg26 mice displayed several fold higher concentration of Ang III, a ligand of AT2R. |
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| Keywords: | AT2R AT1R Angiotensin II Angiotensin III HIV-associated nephropathy |
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