Progressive renal vascular proliferation and injury in obese Zucker rats.
OBJECTIVE
Obesity, an independent risk factor for chronic kidney disease, may induce renal injury by promoting inflammation. Inflammatory cytokines can induce neovascularization in different organs, including the kidneys. However, whether obesity triggers renal neovascularization and, if so, its effect on renal function has never been investigated.


METHODS
Blood pressure, proteinuria, and glomerular filtration rate (GFR) were measured in vivo. Renal microvascular (MV) architecture was studied by 3D micro-CT in lean and obese Zucker rats (LZR and OZR, n = 7/group) at 12, 22, and 32 weeks of age. Renal inflammation was assessed by quantifying interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and ED-1 expression, as renal fibrosis in trichrome-stained cross-sections.


RESULTS
Mild inflammation and lower GFR was only observed in younger OZR, without renal fibrosis or changes in MV density. Interestingly, renal MV density increased in OZR at 32 weeks of age, accompanied by pronounced increase in renal IL-6 and TNF-alpha, ED-1+ cells, proteinuria, decreased GFR, and fibrosis.


CONCLUSIONS
This study shows increased renal cortical vascularization in experimental obesity, suggesting neovascularization as an evolving process as obesity progresses. Increased renal vascularization, possibly triggered by inflammation, may reflect an initially compensatory mechanism in obesity. However, increased inflammation and inflammatory-induced neovascularization may further promote renal injury as obesity advances.
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA.
Radu
R
Iliescu
Alejandro R
AR
Chade
D000818:Animals; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate; D006801:Humans; D021621:Imaging, Three-Dimensional; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000098:blood supply* / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D008833:Microcirculation; D009389:Neovascularization, Pathologic; D009765:Obesity / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D011924:Rats, Zucker; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055114:X-Ray Microtomography
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha