Abstract
BackgroundCoronary collateral arteries function as natural bypasses in the event of coronary obstruction. The degree of collateral network development significantly impacts the outcome of patients after an acute myocardial infarction (AMI). MicroRNAs (miRNAs, miRs) have arisen as biomarkers to identify heterogeneous patients, as well as new therapeutic targets in cardiovascular disease. We sought to identify miRNAs that are differentially expressed in chronic total occlusion (CTO) patients with well or poorly developed collateral arteries.Methods and ResultsForty-one CTO patients undergoing coronary angiography and invasive assessment of their coronary collateralization were dichotomized based on their collateral flow index (CFI). After miRNA profiling was conducted on aortic plasma, four miRNAs were selected for validation by real-time quantitative reverse transcription polymerase chain reaction in patients with low (CFI<0.39) and high (CFI>0.39) collateral artery capacity. We confirmed significantly elevated levels of miR423-5p (p<0.05), miR10b (p<0.05), miR30d (p<0.05) and miR126 (p<0.001) in patients with insufficient collateral network development. We further demonstrated that each of these miRNAs could serve as circulating biomarkers to discriminate patients with low collateral capacity (p<0.01 for each miRNA). We also determined significantly greater expression of miR30d (p<0.05) and miR126 (p<0.001) in CTO patients relative to healthy controls.ConclusionThe present study identifies differentially expressed miRNAs in patients with high versus low coronary collateral capacity. We have shown that these miRNAs can function as circulating biomarkers to discriminate between patients with insufficient or sufficient collateralization. This is the first study to identify miRNAs linked to coronary collateral vessel function in humans.
Highlights
Collateral artery growth, a process known as arteriogenesis [1], provides an alternative route for blood perfusion in the event of obstructive coronary artery disease
Forty-one chronic total occlusion (CTO) patients undergoing coronary angiography and invasive assessment of their coronary collateralization were dichotomized based on their collateral flow index (CFI)
After miRNA profiling was conducted on aortic plasma, four miRNAs were selected for validation by real-time quantitative reverse transcription polymerase chain reaction in patients with low (CFI0.39) collateral artery capacity
Summary
Collateral artery growth, a process known as arteriogenesis [1], provides an alternative route for blood perfusion in the event of obstructive coronary artery disease. Previous studies have shown differences in gene expression at messenger RNA (mRNA) level between CAD patients with poor versus well-developed coronary collateral arteries [5, 6]. There is currently limited information on microRNA (miRNA) expression in CAD patients with varying degree of collateral artery formation. Recent studies have identified miRNAs as suitable biomarkers to discriminate patients with cardiovascular diseases, including heart failure, stable CAD, as well as acute myocardial infarction (AMI) [10]. We sought to identify circulating miRNAs that are differentially expressed in chronic total occlusion (CTO) patients with poor and well-developed coronary collateral arteries. We sought to identify miRNAs that are differentially expressed in chronic total occlusion (CTO) patients with well or poorly developed collateral arteries
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