Analysis of circulating miRNA levels at the transition from compensated cardiac hypertrophy to heart failure: identification of possible biomarkers of heart failure

Abstract

Heart failure (HF) is a complex clinical syndrome that can arise as a consequence of a broad spectrum of structural and functional cardiac abnormalities. Cardiac hypertrophy as a consequence of hypertension is a compensatory mechanism that initially protects the heart, but excessive work overload is an important predictor of HF. Despite the importance of hypertrophy as a risk factor for the development of HF, not all hypertrophied hearts will ultimately fail and develop HF. Possibly, hearts prone to HF are discernible at the molecular level already in the early stages of the disease, before the transition to HF has occurred. If hypertrophied hearts prone to the development of HF express early molecular signals of this propensity, this property would provide an opportunity to identify these individuals prone to the development of HF even at an early stage of the disease, which will allow further medical intervention during the progression of the disease. Monitoring of the progression of heart disease is done through imaging tests such as echocardiography, cardiac biopsies and also through serum biomarkers of cardiac stress, such as natriuretic peptide type B (BNP) and its amino-terminal fragment, NT-pro -BNP. However, the greatest efficiency of these biomarkers is when cardiac injury is already established and factors such as age, renal function and obesity mask some results. Thus, there is an effort to identify new biomarkers that could detect myocardial damage early. Because of their stability in circulation, microRNAs (miRNAs) are currently being exploited for their potential as biomarkers for various diseases. Using an experimental model of cardiac hypertrophy, we showed that 70% of the animals maintained their hearts hypertrophied associated with preserved cardiac function, while 30% developed HF associated with systolic and diastolic dysfunction after 90d of abdominal aortic constriction. Now, our focus is to identify those individuals who will progress to HF through the analysis of miRNA in the blood. If we can identify changes in the circulating miRNAs levels in the compensatory phase that could identify which animals will develop HF, these miRNAs could serve as biomarkers and indicate possible target biological pathways in the prevention of heart failure as a consequence of cardiac hypertension/hypertrophy. (AU)