ABSTRACT
Objective: External counterpulsation (ECP) provides long-term benefits of improved anginal frequency and exercise tolerance in patients with refractory angina (RA). This is postulated as a result of improved angiogenesis and endothelial function through an increase in shear stress. Angiogenesis is mainly represented by vascular endothelial growth factor-A (VEGF-A) and its receptor, vascular endothelial growth factor receptor-2 (VEGFR-2). The microRNA-92a (miR-92a) is a flow-sensitive miRNA that regulates atherosclerosis and angiogenesis in response to shear stress. Thus, ECP beneficial effect might be achieved through interaction between VEGF-A, VEGFR-2, and miR-92a. This study aims to evaluate the ECP effect on VEGF-A, VEGFR-2, and miR-92a in patients with RA in a sham-controlled manner. Methods: This was a randomized sham-controlled trial, enrolling 50 patients with RA who have coronary artery disease (CAD). Participants were randomized (1:1 ratio) to 35 sessions of either ECP (n = 25) or sham (n = 25), each session lasting for 1 h. Plasma levels of VEGF-A and VEGFR-2 were assayed by the ELISA technique. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to measure miR-92a circulating levels in plasma. Result: External counterpulsation significantly preserved VEGF-A and VEGFR-2 level compared to sham [ΔVEGF-A: 1 (-139 to 160) vs.-136 (-237 to 67) pg/ml, p = 0.026; ΔVEGFR-2: -171(-844 to +1,166) vs. -517(-1,549 to +1,407) pg/ml, p = 0.021, respectively]. Circulating miR-92a increased significantly in ECP [5.1 (4.2-6.4) to 5.9 (4.8-6.4), p < 0.001] and sham [5.2 (4.1-9.4) to 5.6 (4.8-6.3), p = 0.008] post-intervention. The fold changes tended to be higher in ECP group, although was not statistically different from sham [fold changes ECP = 4.6 (0.3-36.5) vs. sham 2.8 (0-15), p = 0.33)]. Conclusion: External counterpulsation improved angiogenesis by preserving VEGF-A and VEGFR-2 levels. Both ECP and sham increased miR-92a significantly, yet the changes were not different between the two groups. (Study registered on www.clinicaltrials.gov, no: NCT03991871, August 8, 2019, and received a grant from the National Health Research and Development of Ministry of Health of Indonesia, No: HK.02.02/I/27/2020).
ABSTRACT
OBJECTIVE: Pro-inflammatory stimuli induce a variety set of microRNAs (miRs) expression that regulate long pentraxin-3 (PTX3) protein, which associates with a procoagulant state in the endothelial cells. We evaluated, for the first time in human, the association of miR-224-3p and miR-155-5p expressions with plasma PTX3 concentration and coronary microvascular obstruction (MVO) in patients with acute ST-segment elevation myocardial infarction (STEMI) with symptom onset ≤ 12 h and treated by primary angioplasty. Blood samples for miRs and PTX3 measurement were drawn at emergency department presentation, and were measured by TaqMan real-time PCR and human ELISA kit, respectively. RESULTS: Of the 217 patients (median age: 54 years, male: 88%), 130 (60%) had angiographic MVO. Spearman analysis showed no correlation between miR-224-3p and miR-155-5p expressions with plasma PTX3 concentration. After adjustment with sex, age, diabetes mellitus, and plasma PTX3 concentration, miR-224-3p ≥ median group was associated with angiographic MVO (odds ratio, 2.60; 95% confidence interval, 1.24 to 5.44, p = 0.01). This study suggests that miR-224-3p and miR-155-5p expressions did not correlate with plasma PTX3 concentration. However, miR-224-3p expression associates with angiographic MVO following primary angioplasty for STEMI. Future studies are needed to identify the specific gene/protein related with miR-224-3p expression in MVO.
