Publication: Modulation of renin angiotensin system predominantly
alters sclerotic phenotype of glomeruli in HIVAN
Authors
Plagov, Andrei ; Lan, Xiqian ; Rai, Partab ; Kumar, Dileep ; Lederman, Rivka ; Rehman, Shabina ; Malhotra, Ashwani ; Ding, Guohua ; Chander, Praveen N. ; Singhal, Pravin C.
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Publisher
F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología
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DOI
https://doi.org/10.14670/HH-29.1575
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info:eu-repo/semantics/article
Description
Abstract
HIV-associated nephropathy (HIVAN) is a
common complication of HIV-1 infection in patients
with African ancestry in general and with APOL1 gene
risk variants in particular. Although collapsing
glomerulopathy is considered a hallmark of HIVAN,
significant numbers of glomeruli in patients with
HIVAN also display other variants of focal segmental
glomerulosclerosis (FSGS). We propose that collapsed
glomeruli as well as glomeruli with other variants of
FSGS are manifestations of HIVAN and their prevalence
depends on associated host factors. We explored the role
of the renin-angiotensin system (RAS) in the
manifestation of any specific glomerular phenotype in
HIVAN. To evaluate the role of the RAS we have used a
genetically engineered mouse model of HIVAN (Tg26)
with two and four copies of angiotensinogen (Agt) gene
(Tg26/Agt2 and Tg26/Agt4). In Tg26/Agt2, 1 out of 6
glomeruli exhibited sclerosed phenotype, whereas 1 out
of 25 glomeruli displayed collapsed phenotype; on the
other hand, in Tg26/Agt4, 1 out of 3 glomeruli exhibited
sclerotic phenotype and only 1 out of 7 glomeruli
showed collapsed phenotype. To inhibit the effect of
RAS, Tg26/Agt2 were administered captopril, aliskiren,
aliskiren plus captopril or aliskiren plus telmisartan by
miniosmotic pumps for 4 weeks. In all experimental
groups there was a significant reduction in percentage of
sclerosed glomeruli and only minimal reduction in
collapsed glomeruli compared to normal saline receiving
Tg26/Agt2. These findings suggest that the
manifestation of the sclerosed phenotype in HIVAN is
predominantly dependent on activation of the RAS.
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Citation
Histology and Histopathology, Vol. 29, n.º 12 (2014)
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