Telomere length in cardiovascular disease; differential expression and prognostic value
04 / 2007 - 02 / 2010
Hart- en vaatziekten treden op bij veroudering, maar niet bij iedereen op hetzelfde moment. De onderzoekers denken dat dit komt door biologische veroudering van DNA in cellen. Zij gaan dit fenomeen bestuderen in patiënten met aderverkalking en hartfalen.
BackgroundI hypothesize that a chromosomal mechanism, telomere length, marks biological aging and underlies the origins of age-related cardiovascular disease. Telomeres are the distal ends of chromosomes. Erosion of telomere leads to an increasingly vulnerable structural integrity of chromosomes. When telomeres reach a critical length, cells become genomically unstable and dysfunctional. I recently demonstrated cross-sectionally that telomere length of circulating white blood cells is shorter in patients with atherosclerosis and chronic heart failure (n=620) as compared to healthy age-matched controls (n=183). The important question emerges whether telomere length of white blood cells biologically reconcile a causal relationship with cardiovascular disease or mark telomere length of other cell types (e.g. endothelial progenitor, or vascular cells).AimsTo determine whether telomere length is differentially expressed a.) among subgroups of white blood cells, and b.) between white blood cells and cardiovascular tissue in patients with and without cardiovascular disease. To determine whether telomere length predicts future cardiovascular events in a.) healthy individuals, and b.) patients with cardiovascular disease at baseline.Methods / Research planTelomere length will be determined by a new high trough-put assay based on a real-time PCR recently further developed and sophisticated by myself (as PhD-student). This is a highly reliably and rapid determination of telomere length. I designed 3 studies. Study 1; focussed on possible telomere length differences among subpopulations of white blood cells (including endothelial progenitor cells, a repair mechanisms in atherosclerosis) in patients with and without cardiovascular disease. Study 2; focussed on telomere length differences in white blood cells versus cardiovascular tissue. Additionally, follow-up will learn the relationship of telomere length (both of tissue and white blood cells) with future cardiovascular events. Study 3; focussed on the relationship of telomere length of healthy individuals (both men and women) and the development of future cardiovascular events.