Enhanced renal cortical vascularization in experimental hypercholesterolemia.
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 microm 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.
Bentley
Michael D
MD
Department of Internal Medicine, Division of Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Rodriguez-Porcel
Martin
M
Lerman
Amir
A
Sarafov
Mirit Hershman
MH
Romero
J Carlos
JC
Pelaez
Laura I
LI
Grande
Joseph P
JP
Ritman
Erik L
EL
Lerman
Lilach O
LO
D000818:Animals; D001808:Blood Vessels / Q000473:pathology; D005260:Female; D006937:Hypercholesterolemia / Q000503:physiopathology*; D007668:Kidney / Q000473:pathology; D007672:Kidney Cortex / Q000098:blood supply* / Q000473:pathology; D008833:Microcirculation; D009389:Neovascularization, Pathologic / Q000209:etiology*; D013552:Swine