Circulating MicroRNAs Characterizing Patients with Insufficient Coronary Collateral Artery Function.
BACKGROUND
Coronary 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.


RESULTS
Forty-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.


CONCLUSIONS
The 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.
Department of Biomedical Engineering & Physics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Nazanin
N
Hakimzadeh
Department of Surgery, University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden, University Medical Center, Leiden, The Netherlands.
A Yaël
AY
Nossent
Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Anja M
AM
van der Laan
Department of Cardiology, Klinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany.
Stephan H
SH
Schirmer
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Maurice W J
MW
de Ronde
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Sara-Joan
SJ
Pinto-Sietsma
Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands.
Niels
N
van Royen
Department of Surgery, University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden, University Medical Center, Leiden, The Netherlands.
Paul H A
PH
Quax
Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Imo E
IE
Hoefer
Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Jan J
JJ
Piek
D000368:Aged; D003097:Collateral Circulation / Q000235:genetics*; D003331:Coronary Vessels / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000145:classification; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged
D035683:MicroRNAs