Project name: Rattus norvegicus

Description: Previous studies showed that aging in coronary arteries is associated with pro-inflammatory phenotypic changes and decreased NO bioavailability, which, we hypothesized, promotes vascular disease by inducing endothelial apoptosis. To test this hypothesis we characterized pro-apoptotic alterations in the phenotype of coronary arteries of aged (26 month old) and young (3 month old) F344 rats. DNA fragmentation analysis and TUNEL assay showed that in aged vessels there was a ~4 fold increase in the number of apoptotic endothelial cells. Analysis of the expression of apoptosis-related genes (microarray, real-time PCR) showed that in aged coronary arteries there was an increased expression of TNFa, TNFb, caspase 9 and an increased presence of cleaved caspase 3 and caspase 9 (Western blotting), whereas expression of TNFR1 and that of TRADD, Bcl-2, Bcl-X(L), Bid, Bax, caspase 8 and caspase 3 were unchanged. We propose that aging-induced up-regulation of TNFa and decreased bioavailability of NO promote endothelial apoptosis in coronary arteries that may lead to the development of endothelial dysfunction and ischemic heart disease in the elderly.Keywords: repeat sample

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: ModelOrganism

Release date: 2003-10-28

Last updated: 2003-08-30