Session Date & Time: None. Available on demand.
*Purpose: The role of aging and hypercholesterolemia (HC) on endothelial cells (ECs) are not well defined. Aged ECs might produce less NO and VEGF, resulting in reduced glomerular capillaries (GCs) and peritubular capillaries (PTCs). Chronic ischemia as a result of decreasing capillaries is considered a significant factor for renal injury. To understand whether the capillary loss was due to changes in angiogenic factors affected by age and cholesterol, we investigated the impact of age and cholesterol on the density of GCs and PTCs.
*Methods: Among 150 patients, 63 (42%) had HC. Antibodies CD31 and HLA-DR stained to determine the mean number of GCs and PTCs. PCNA, VEGF, and NO expression of GCs and PTCs examined. EC proliferation index (PI) of GCs and PTCs assessed by PCNA. Villin expression and PI of tubules examined. Follow-up biopsies analyzed for the development of interstitial fibrosis (IF) and glomerulosclerosis (GS).
*Results: The mean capillary numbers were 38,4±15,2 and 27,6±14,4 for GCs and PTCs, respectively. VEGF and NO expression of both GCs and PTCs and the PI of all capillaries decreased with increasing donor age and cholesterol (p<0.001). The PI index of ECs showed a negative correlation with the VEGF and NO expression of both GCs and PTCs (p<0.001). The number of PTCs correlated with PTCitis (r= -0,73, P<.001), PTC-VEGF expression (r= 0,73, P<0,001), PTC-NO expression (r= 0,86, P<0.001), tubular villin expression (r= -0,83, P<.001), proteinuria (r= -0,49, P<.001), hypertension (r= -0,48, P<.001), development of IF (r= -0,74, P<0.001), graft loss (r=-0,57, P<.001). The GC loss was also significantly associated with GC inflammation (r= -0,68, P<.001), GC-VEGF expression (r=0,76, P<.001), GC-NO expression (r=0,86, P<.001), tubular villin expression (r= -0,76, P<.001), proteinuria (r= -0,64, P<.001), hypertension (r= -0,43, P<.001), development of GS (r= -0,53, P<.001), graft loss (r= -0,46, P<.001).
*Conclusions: A marked loss of capillary VEGF and NO expression associated with aging and HC resulted in a significant loss of GCs and PTCs. The loss of PTCs and GCs significantly correlated with the severity of the tubular injury, proteinuria, hypertension, development of IF and GS. We suggested that donor age and HC influenced graft survival negatively by impairing the microvasculature and tubular integrity in renal allografts.
To cite this abstract in AMA style:Ozdemir B, Akcay E, Atilgan AOk, Haberal M. Hypercholesterolemia and Donor Age Impaired Capillary Vegf and Nitric Oxide (no) Expression and in Turn Decrease Both Microvascular Density and Tubule Villin Expression in Renal Allografts, Resulting in Poor Graft Survival [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/hypercholesterolemia-and-donor-age-impaired-capillary-vegf-and-nitric-oxide-no-expression-and-in-turn-decrease-both-microvascular-density-and-tubule-villin-expression-in-renal-allografts-resulting/. Accessed June 13, 2021.
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