Diagnostic Utility and Pathogenic Role of Circulating MicroRNAs in Vasospastic Angina.

Chan Soon Park,Hyun-Jai Cho,Han-Mo Yang,Jung-Kyu Han,Gyu Chul Oh,Woo-Young Chung,Kyung Woo Park,Bon-Kwon Koo,Hae-Young Lee,Inho Kim,Seil Oh,Hyun-Jae Kang

doi:10.3390/jcm9051313

Abstract

We investigated the diagnostic value and pathophysiological role of circulating microRNA (miR) in vasospastic angina (VA). We enrolled patients who underwent coronary angiography for chest pain to explore the miR’s diagnostic utility. In addition, we investigated the role of miRs in regulating endothelial nitric oxide synthase (eNOS) expression in human coronary artery endothelial cells (hCAECs). Among the 121 patients, 46 were diagnosed with VA (VA group), 26 with insignificant coronary lesions (ICL group), and 49 with atherothrombotic angina (AA group). The VA group showed a significantly higher expression of miR-17-5p, miR-92a-3p, and miR-126-3p than the ICL group. In contrast, miR-221-3p and miR-222-3p were upregulated in the AA group compared to the VA group, and all levels of miR-17-5p, miR-92a-3p, miR-126-3p, miR-145-5p, miR-221-3p, and miR-222-3p differed between the AA group and the ICL group. In the hCAECs, transfection with mimics (pre-miR) of miR-17-5p, miR-92a-3p, and miR-126-3p was associated with eNOS suppression. Additionally, transfection with inhibitors (anti-miR) of miR-92a-3p significantly rescued the eNOS suppression induced by lipopolysaccharide. In conclusion, the circulating miRs not only proved to have diagnostic utility, but also contributed to pathogenesis by eNOS regulation.

Highlights

Vasospastic angina (VA), caused by dynamic occlusion of the major epicardial coronary artery, is characterized by resting chest pain accompanied by transient ST segment deviation on electrocardiography, but the coronary artery shows normal appearance on resting coronary artery angiography (CAG) [1,2]
We evaluated the impact of miRs in regulating the endothelial nitric oxide synthase expression using human coronary artery endothelial cells
There was no significant difference in the prevalence of cardiovascular risk factors, such as hypertension, hyperlipidemia, chronic kidney disease, and smoking history, while the AA group showed high prevalence of diabetes mellitus

Summary

Introduction

Vasospastic angina (VA), caused by dynamic occlusion of the major epicardial coronary artery, is characterized by resting chest pain accompanied by transient ST segment deviation on electrocardiography, but the coronary artery shows normal appearance on resting coronary artery angiography (CAG) [1,2]. VA occurs in young or middle-aged patients who are considered to be at low risk of cardiovascular disease [5]; it is often difficult to distinguish VA from other causes through the medical history alone. Clinical guidelines recommend considering VA in the aforementioned patients and in those with persistent angina and in those with symptoms after percutaneous coronary intervention. In the cases of those with chest pain but without a fixed atherothrombotic lesion in coronary angiography, the provocation test should be considered to rule out VA. Patients with chest pain are often treated with vasodilators to relieve symptoms and signs of myocardial ischemia, and these patients have to reschedule the CAG with a provocation test after abstaining from vasodilators for 24–48 h. Noninvasive echocardiography with pharmacological provocation has been used in some institutes [8], the lack of coronary artery access can be life-threatening

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