title: Adverse host factors exacerbate occult HIV-associated nephropathy.
abstract: In the present study, we hypothesized that HIV-1-induced occult HIV-associated nephropathy (HIVAN) would become apparent in the presence of adverse host factors. To test our hypothesis, Vpr mice (which display doxycycline-dependent Vpr expression in podocytes) with two, three, and four copies of the angiotensinogen (Agt) gene (Vpr-Agt-2, Vpr-Agt-3, and Vpr-Agt-4) were administered doxycycline for 3 weeks (to develop clinically occult HIVAN) followed by doxycycline-free water during the next 3 weeks. Subsequently, renal biomarkers were measured, and kidneys were harvested for renal histology. Vpr-Agt-2 developed neither proteinuria nor elevated blood pressure, and displayed minimal glomerular and tubular lesions only, without any microcyst formation. Vpr-Agt-3 showed mild glomerular and tubular lesions and microcyst formation, whereas Vpr-Agt-4 showed moderate proteinuria, hypertension, glomerular sclerosis, tubular dilation, microcysts, and expression of epithelial mesenchymal transition markers. Vpr-Agt-4 not only displayed enhanced renal tissue expression of Agt, renin, and angiotensin-converting enzyme, but also had higher renal tissue concentrations of angiotensin II. Moreover, renal cells in Vpr-Agt-4 showed enhanced expression of transforming growth factor-β, connective tissue growth factor, and vascular endothelial growth factor. These findings indicate that adverse host factors, such as the activation of the renin-angiotensin system, promote the progression of occult HIVAN to apparent HIVAN.
authors.affiliation: Department of Medicine, North Shore-Long Island Jewish Health System, New Hyde Park, New York, NY 11021, USA.
authors.forename: Dileep
authors.initials: D
authors.lastname: Kumar
authors.forename: Divya
authors.initials: D
authors.lastname: Salhan
authors.forename: Sandeep
authors.initials: S
authors.lastname: Magoon
authors.forename: Deepti D
authors.initials: DD
authors.lastname: Torri
authors.forename: Swapna
authors.initials: S
authors.lastname: Sayeneni
authors.forename: Ankita
authors.initials: A
authors.lastname: Sagar
authors.forename: Anshu
authors.initials: A
authors.lastname: Bandhlish
authors.forename: Ashwani
authors.initials: A
authors.lastname: Malhotra
authors.forename: Praveen N
authors.initials: PN
authors.lastname: Chander
authors.forename: Pravin C
authors.initials: PC
authors.lastname: Singhal
mesh_terms: D016263:AIDS-Associated Nephropathy / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D000804:Angiotensin II / Q000378:metabolism; D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D004318:Doxycycline / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D016334:Genes, vpr; D054884:Host-Pathogen Interactions / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010641:Phenotype; D011507:Proteinuria / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015415:Biomarkers; C526318:CCN2 protein, mouse; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D000808:Angiotensinogen; D000804:Angiotensin II; D055513:Connective Tissue Growth Factor; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D004318:Doxycycline