TY - JOUR
T1 - Enhanced renal cortical vascularization in experimental hypercholesterolemia
AU - Bentley, Michael D.
AU - Rodriguez-Porcel, Martin
AU - Lerman, Amir
AU - Hershman Sarafov, Mirit
AU - Romero, J. Carlos
AU - Pelaez, Laura I.
AU - Grande, Joseph P.
AU - Ritman, Erik L.
AU - Lerman, Lilach O.
N1 - Funding Information:
This study was supported in part by grants HL-03621, HL-63282, and RR-11800 from the NIH, and by the Mayo Foundation. The authors are grateful to the following individuals for their skillful technical assistance: Mr. James D. Krier, Ms. Denise A. Reyes, Mr. Steven M. Jorgensen, Ms. Patricia E. Lund, Ms. Paula Carlson, and Ariel Feldstein, MD. The authors would also like to thank Ms. Julie M. Patterson for her assistance with the preparation of illustrations.
PY - 2002/3
Y1 - 2002/3
N2 - 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.
AB - 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.
KW - Hypercholesterolemia
KW - Kidney
KW - Micro computed tomography
KW - Microcirculation
KW - Neovascularization
UR - http://www.scopus.com/inward/record.url?scp=0036183670&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036183670&partnerID=8YFLogxK
U2 - 10.1046/j.1523-1755.2002.00211.x
DO - 10.1046/j.1523-1755.2002.00211.x
M3 - Article
C2 - 11849461
AN - SCOPUS:0036183670
SN - 0085-2538
VL - 61
SP - 1056
EP - 1063
JO - Kidney international
JF - Kidney international
IS - 3
ER -