Circulating miR-208b and miR-34a Are Associated with Left Ventricular Remodeling after Acute Myocardial Infarction

Abstract

Left ventricular remodeling after acute myocardial infarction (AMI) is associated with adverse prognosis. It is becoming increasingly clear that circulating miRNAs could be promising biomarkers for various pathological processes in the heart, including myocardial infarction, myocardial remodeling and progression to heart failure. In the present study, a total of 359 consecutive patients were recruited. Plasma samples were collected on admission. Echocardiographic studies were performed during the admission and at six months follow-up after AMI. Remodeling was defined as an at least 10% increase from baseline in the left ventricular end-diastolic volume. Plasma miRNA levels were assessed for association with six months mortality or development of heart failure. Results showed that levels of plasma miR-208b and miR-34a were significantly higher in patients with remodeling than those without. Increased miRNA levels were strongly associated with increased risk of mortality or heart failure within six months for miR-208b (OR 17.91, 95% confidence interval = 2.07–98.81, p = 0.003), miR-34a (OR 4.18, 95% confidence interval = 1.36–12.83, p = 0.012) and combination of the two miRNAs (OR 18.73, 95% confidence interval = 1.96–101.23, p = 0.000). The two miRNA panels reclassified a significant proportion of patients with a net reclassification improvement of 11.7% (p = 0.025) and an integrated discrimination improvement of 7.7% (p = 0.002). These results demonstrated that circulating miR-208b and miR-34a could be useful biomarkers for predicting left ventricular remodeling after AMI, and the miRNA levels are associated with increased risk of mortality or heart failure.

Novel heart failure biomarkers: why do we fail to exploit their potential?

“…For example, myocardial and circulating miRNA-21 were both associated with the degree of myocardial fibrosis [167]. Several other studies showed associations between circulating miRNAs, including miR-20a, miR208b, and miR-34a, and processes of cardiac remodeling, making them potentially interesting biomarkers [168,169]. The miRNAs, miR-22-3p, miR148b-3p, and miR-409-3p, were also associated with HF [170,171].…”

Expression of circulating microRNA in chronic heart failure in patients with cardiovascular pathologies

“…Повышенное содержание микроРНК-423-5р у больных с ХСН, вызванной ВКМП, по отношению к группе сравнения может свидетельствовать о кардиальном генезе этой ми-кроРНК и выходом ее в кровоток при повреждении миокарда, что подтверждается недавними работами C. Bauters, E. Nabiałek, L. Goldraich [17][18][19]. По-вышенный уровень микроРНК-34а относительно подгруппы ДГС, возможно, связан с преобладанием процессов ремоделирования ЛЖ после ИМ у паци-ентов группы сравнения [12].…”

“…Подавление экспрессии этой микроРНК приводило к сниже-нию гипертрофии, фиброза, апоптоза стареющих клеток и улучшало восстановление миокарда в мо-дели животных после инфаркта миокарда (ИМ). Также уровень циркулирующей микроРНК-34а может быть использован в качестве прогностиче-ского биомаркера ремоделирования левого желу-дочка (ЛЖ) после ИМ [12]. МикроРНК-208a и 499 являются миокардиоспецифичными.…”

Left Ventricular Remodeling after Acute Myocardial Infarction and Biomarkers

“…MiR-208b is characterized as cardiac-specific microRNA in early diagnosis of AMI and where showed a correlation between plasma miR-208b and LV dysfunction after MI. Despite miR-34 family has protective attribute against pathological cardiac remodeling, though overexpression of miR-34a demonstrates induced endothelial cells aging and atherosclerosis [24].…”