Enhanced renal cortical vascularization in experimental hypercholesterolemia

Michael D. Bentley, Martin Rodriguez-Porcel, Amir Lerman, Mirit Hershman Sarafov, J. Carlos Romero, Laura I. Pelaez, Joseph P. Grande, Erik L. Ritman, Lilach O. Lerman

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Background. Experimental hypercholesterolemia is associated with pro-inflammatory changes and impaired regulation of tissue perfusion, which may lead to neovascularization. However, it is yet unknown whether such changes take place in the kidney. In this study, using a novel three-dimensional (3-D) micro computed-tomography technique we tested the hypothesis that hypercholesterolemia was associated with increased microvascular density in the renal cortex. Methods. Kidneys were excised from pigs after 12 weeks of either a normal (N = 6) or high cholesterol (HC; N = 5) diet, histology slides processed, and a segmental renal artery injected with a radio-opaque intravascular silicone polymer. Renal samples were scanned with micro computed-tomography, transverse and three-dimensional images were reconstructed, and microvessels (80 to 360 μm in diameter) counted in situ. Results. Serum cholesterol levels were significantly higher in hypercholesterolemic compared to normal pigs (383 ± 76 vs. 81 ± 7 mg/dL, P < 0.01), and microvascular spatial density was significantly higher in their inner and middle renal cortex (189 ± 7 vs. 126 ± 6 microvessels/cm2, P < 0.0001). Hypercholesterolemic kidneys also showed mild interstitial mononuclear infiltration and heavier immunostaining of vascular endothelial growth factor, but no other signs of morphological damage. Conclusions. These results demonstrate that early diet-induced hypercholesterolemia is associated with increased microvascular density in the renal cortex, which precedes signs of overt renal morphological damage. These alterations may potentially affect regulation and/or spatial distribution of intrarenal blood flow in hypercholesterolemia, and may participate in renal disease progression.

Original languageEnglish (US)
Pages (from-to)1056-1063
Number of pages8
JournalKidney international
Volume61
Issue number3
DOIs
StatePublished - Mar 2002

Keywords

  • Hypercholesterolemia
  • Kidney
  • Micro computed tomography
  • Microcirculation
  • Neovascularization

ASJC Scopus subject areas

  • Nephrology

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