title: Increased capillary branching contributes to angiotensin type 1 receptor blocker (ARB)-induced regression of sclerosis.
abstract: Chronic kidney disease is characterized by progressive glomerulosclerosis and tubulointerstitial fibrosis. High-dose angiotensin type 1 receptor blocker (ARB) or angiotensin-converting enzyme inhibitor can induce regression of existing glomerulosclerosis, at least in part by decreasing matrix accumulation. However, the potential mechanisms of remodeling of capillary loops remain obscure. This study aimed to determine whether capillary branching was augmented in glomeruli with ARB-induced regression of sclerosis. Three-dimensional confocal images were assessed by graph theory analysis to explore the topology of the glomerular capillary network. Compared with normal glomeruli, glomeruli of rats with progressive sclerosis were enlarged but had a significantly reduced number of capillary segments and capillary branch points and decreased complexity of the glomerular network. In contrast, in rats with regression of sclerosis induced by ARB, glomerular enlargement was due to a significantly increased number of glomerular capillary segments and capillary branch points and restored complexity of the capillary network. These data support the theory that capillary growth contributes to regression of sclerosis and is mediated at least in part by ARB-induced increased complexity and branching of capillary segments.
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Scruggs
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Zuo
authors.forename: Ellen
authors.initials: E
authors.lastname: Donnert
authors.forename: Lijun
authors.initials: L
authors.lastname: Ma
authors.forename: John F
authors.initials: JF
authors.lastname: Bertram
authors.forename: Agnes B
authors.initials: AB
authors.lastname: Fogo
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D002196:Capillaries / Q000378:metabolism; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy*; D006801:Humans; D021621:Imaging, Three-Dimensional; D007678:Kidney Glomerulus / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D012598:Sclerosis / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers