Interleukin-1 receptor antagonist (IL-1RN) genotype modulates the replicative capacity of human endothelial cells

Dewberry, Rachael M., Crossman, David C. and Francis, Sheila E. (2003) Interleukin-1 receptor antagonist (IL-1RN) genotype modulates the replicative capacity of human endothelial cells. Circulation Research, 92 (12). pp. 1285-1287. ISSN 0009-7330

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Abstract

Endothelial cells (ECs) undergo a finite number of cell divisions before growth arrest or replicative senescence, modulated in part by the proinflammatory cytokine, interleukin-1 (IL-1). IL-1 and its family members are expressed in human atherosclerotic vessels, mainly in the endothelium. EC replicative senescence and IL-1 have been associated with atherosclerosis. Genetic variants at the IL-1 locus have been associated with a variety of coronary phenotypes. In this study, we examined the relationship between the interleukin-1 receptor antagonist variable number tandem repeat allele 2 (IL-1RN*2*2) and EC replicative capacity. A significant decrease in EC cumulative population doublings (CPDs) was associated with the rare allele (IL-1RN*2*2) at IL-1RN, 8.56±0.97 (n=7) versus 13.14±1.00 (IL-1RN*1*1, n=20), P=0.0118. Proliferation of IL-1RN*2*2 ECs detected by Ki67 expression was also significantly reduced particularly at later passage, passage 6: 21.76±0.93% (n=6) versus 48.10±8.81% (IL-1RN*1*1, n=7) (P=0.0323) and passage 8: 22.48±3.08% (n=6) versus 42.29±3.06% (IL-1RN*1*1, n=7) (P=0.0028). IL-1RN*2 carriage was associated with increased numbers of senescent ECs. Basal apoptosis, telomerase activity, and telomere length were not different with respect to IL-1RN genotype. Addition of exogenous IL-1ra (1 ng/mL) increased CPDs in a number of human umbilical vein endothelial cell cultures and increased proliferating cells from 12.11±1.21% to 27.82±2.82% (P=0.0216, IL-1RN*2*2, passage 8, n=2). These data suggest genetic control of EC proliferation and life span by the IL-1 locus and imply that IL-1ra may have a function connected with EC growth.

Item Type:	Article
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Norwich Clinical Trials Unit
Depositing User:	Rhiannon Harvey
Date Deposited:	17 May 2011 15:15
Last Modified:	07 Mar 2023 17:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/30691
DOI:	10.1161/01.RES.0000078172.52740.9B

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