Abstract 44: Global Hypomethylation and Promoter Hypomethylation of Flt1 Concurrently Occurred Iin Atherosclerotic Tissues
Background and objectives: Epigenetic alterations have been suggested as a pathological mechanism in atherosclerosis development. However, global and gene-specific epigenetic changes have not been well-known in atherosclerotic tissues yet. We evaluated whether the global methylation and promoter methylation of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) genes of atherosclerotic tissues was different from peripheral leukocytes in carotid stenosis patients.
Methods: We used carotid endarterectomy (CEA) tissues and peripheral leukocytes (WBC) collected from 27 patients, who received CEA to remove athoerslcerotic plaque from proximal internal carotid artery. To evaluate global methylation status in the CEA tissue and WBC of each patient, pyrosequencing for long-interspersed nuclear element (LINE) sequence was performed. The evaluation of gene-specific promoter methylation status targeted to angiogenesis-related genes including VEGF, VEGFR1 (Flt1), and VEGFR2 (KDR). The methylation status of each gene was evaluated using methylation specific polymerase chain reaction. The differences of global and gene-specific methylation status of each tested gene were compared between CEA and WBC of all patients.
Results: On global methylation status evaluation, LINE methylation was lower in CEA than WBC (CEA, 63.7±1.7; WBC, 65.8±3.3%, p=0.002). CEA tissues also showed significantly lower promoter methylations in VEGFR1 (CEA, 5.3±7.1; WBC, 11.9±9.4%, p=0.007). The methylation status of VEGFR2 (CEA, 21.4±11.5; WBC, 25.5±13.5%, p=0.220) and VEGF (CEA, 19.3±11.8; WBC, 18.0±9.9%, p=0.561) was not statistically different between CEA and WBC samples of the patients.
Conclusion: The concurrent decrease pattern of LINE and VEGFR1 suggested that the hypomethylation occurred globally and gene-specifically in angiogenesis-related genes of proximal ICA stenosis. In particular, the VEGFR1 promoter hypomethylation in atherosclerotic tissues might be an epigenetic evidence to explain the increase of angiogenesis increasing inside of atherosclerotic plaque.
Author Disclosures: J. Kim: None. J. Hwang: None. H. Jeong: None. S. Kwon: None. G. Kim: None. J. Kim: None.
- © 2014 by American Heart Association, Inc.