Abstract 15243: Beta-Blockers Regulate Atherosclerosis-Relevant Gene Products in Carotid Plaques at the Transcriptional Level
Background: Beta receptor blockade (BRB) and statin treatment (ST) are used to prevent perioperative cardiovascular events. The mechanism of action is still debated. Direct effects of ST on endothelial function and of BRB on heart rate are deemed causative. Transcriptional effects have scarcely been investigated in this setting. Heme oxygenase-1 (HO-1) and CCL2 have been shown to be transcriptionally regulated by statins and have recently been described to drive plaque stability, while effects of BRB on transcriptional regulation have not been examined. We have compared the effect of chronic ST and BRB on CCL2 and HO-1-expression in carotid plaques.
Methods: With permission of the IRB thrombendarterectomy specimens were collected on RNAlater, divided into rings and frozen in liquid nitrogen. Tissue homogenization was performed before chloroform/phenol-based RNA extraction. RNA-quality assessed by chip electrophoresis yielded RIN-values between 2.5 and 4.5. Target-PCR normalized for PCR efficiency and the three most stable house keeping genes (GAPDH, ATPsynthase, Tubulin) using qBase software yielded robust reproducibility and plausible fluctuations of target gene expression (VCAM, collagen, CD14) if stable lesions were compared to unstable lesions (Virmani II vs IV).
Results: From 110 consecutive carotid thrombendarterectomy patients (63±13 y; 67.5% male) informed consent was obtained. ST was present in 40 hypercholesterolemic patients, 37 patients were on BRB for ischemic heart disease or cardiac failure, while 33 patients had neither. No significant differences in age or sex distribution were detected between the groups. CCL2 expression was reduced in BRB- more than in ST-patients (1.9±0.35 vs 1.6±0.2 vs 1.0±0.17, none vs ST vs BRB, p<0.01). HO-1 induction was more pronounced in BRB- compared to ST-patients (0.85±0.11 vs 1.72±0.5 vs 3.07±0.7; none vs ST vs BRB, p<0.01).
Conclusions: Previously described effects of chronic ST on transcriptional regulation of atherosclerosis-associated genes can be detected in plaques. BRB treatment is associated with transcriptional effects on the same gene products, suggesting that a critical reevaluation of the mechanism of perioperative BRB is necessary and may yield novel therapeutic targets.
- © 2010 by American Heart Association, Inc.