Abstract P244: MicroRNAs Implicated in Angiogenesis Are Upregulated in Lower Extremity Peripheral Artery Disease (PAD): the San Diego Population Study (SDPS)
Introduction: Lower extremity PAD affects approximately 9 million people in the US. However, the genetic factors underlying PAD remain elusive. MicroRNAs are short non-coding RNA segments that regulate gene expression post-transcriptionally. MicroRNAs are hypothesized to be involved in angiogenesis, inflammation, and immune processes central to atherosclerotic process, are modifiable, and thus have potential as therapeutic targets. No previous studies have assessed the role of microRNAs in PAD in a population-based sample.
Methods: The SDPS is a prospective population-based cohort of non-Hispanic White, African-American, Hispanic and Asian men and women designed to study PAD and venous disease. A sex- and age-matched nested sample of 24 PAD cases and 24 controls were chosen from 1103 participants who attended the 2007-11 exam. PAD was defined as ankle brachial index (ABI)<0.90, while the ABI range for controls was 1.1-1.3. Thirty-five microRNAs hypothesized to be of importance in development of atherosclerosis were measured in plasma using a high throughput RT qPCR method on the BioMark microfluidic System. MicroRNA expression levels (Cq values) were compared between PAD cases and controls using linear regression and least squares means, with adjustment for age and sex to remove residual confounding.
Results: Overall mean±SD age was 79±7, with mean ABI among the PAD cases of 0.60±0.12 and among controls was 1.17±0.06.Six microRNAs, miR-181b, -195, -22, -27b, -424, and -503, were significantly upregulated in PAD cases vs. controls (Figure), all p<0.05. Existing evidence indicates that miR-195,-27b, -424, and -503 are involved in angiogenesis, and miR-503 is upregulated in ischemic leg muscle of patients with diabetes.
Conclusions: Individuals with PAD have significantly higher expression of miRNAs linked to angiogenesis.Additional research is needed in larger studies to further assess associations with clinical and subclinical PAD, as well as the viability of these miRNAs as therapeutic targets for PAD.
Author Disclosures: C. Wassel: None. J.E. Freedman: None. K. Tanriverdi: None. P. Durda: None. R.P. Tracy: None. M.A. Allison: None. J.H. Ix: None. J.O. Denenberg: None. M.H. Criqui:None.
- © 2017 by American Heart Association, Inc.