Abstract 569: M-RNA Expressions in Carotid Atherosclerotic Lesions Related to Plasma Levels of Lipoprotein (a)
Objective High plasma levels of Lipoprotein (a), (Lp(a)) is an atherosclerotic risk factor. Individual levels of Lp(a) are genetically determined and constant over lifetime. Thus, individuals with high Lp(a) levels are exposed to this risk factor over a long time. In vitro, Lp(a) has many biochemical and signalling effects which could act proatherogenic, but until now, nothing has been possible to confirm in vivo. Plasma levels of Lp(a) correlate with lesion levels of Lp(a).
Methods A consecutive series of 153 patients operated for Carotid stenosis by Trombendarterectomy (TEA) had plasma samples taken preoperatively. TEA-specimens were analysed for gene expression by Affymetrix. Plasma samples were analysed for levels of Lp(a) with routine antibody-methods. 20000 different m-RNA expression levels were correlated to 10log levels of Lp(a). Patients with plasma levels of Lp(a) above 60mg/dl were compared with those below 20mg/dl
Results The most up regulated gene in patients with high Lp(a) compared to normal/low Lp(a) is MIAT (myocardial infarction associated transcript), also known as RNCR2 (retinal non-coding RNA) or Gomafu, a long non-coding RNA. MIAT is associated with risk of myocardial infarction. The most down regulated gene is Glypican 4, a member of heparane sulfate proteoglycans. Lp(a) binds to proteoglycans. Gene enrichment analysis revealed Lp(a) association with cholesterol efflux, oxygen binding and proteasome complex, each with a role in atherosclerosis.
m-RNA from the LPA-gene could not be detected, confirming previous assumption that apo (a) is not synthesised in vascular tissue.
Conclusions High levels of Lp(a) is associated with gene expression in carotid lesions, some suggestive to a proatherosclerotic pathway. The new finding of association with MIAT and the proteasome complex deserves further studies.
- © 2013 by American Heart Association, Inc.