Altered microRNA expression associated with reduced catecholamine sensitivity in patients with chronic heart failure

作者：Funahashi Hidehito; Izawa Hideo^*; Hirashiki Akihiro; Cheng Xian Wu; Inden Yasuya; Nomura Masanori; Murohara Toyoaki

来源：Journal of Cardiology, 2011, 57(3): 338-344.

DOI：10.1016/j.jjcc.2011.01.009

• Adrenergic receptor
• Heart failure
• Biopsy
• MicroRNA

Aims: MicroRNAs (miRNAs) are small non-coding RNAs discovered as potential new gene regulators. Their roles in the development of chronic heart failure (CHF), however, are largely unknown. Reduced catecholamine sensitivity is an early step of CHF. We examined whether altered expression of miRNAs was related to reduced catecholamine sensitivity in patients with CHF.
Methods and results: Maximum first derivative of left ventricular pressure (LV dP/dt(max)) at baseline and during infusion of dobutamine (10 mu g kg(-1) min(-1)) were determined in 14 asymptomatic or mildly symptomatic (New York Heart Association class I or II) patients with idiopathic dilated cardiomyopathy (DCM). We performed microarray analysis for a total of 485 miRNAs using endomyocardial biopsy specimens from these 14 patients. Patients were classified into 2 groups based on a percent increase in LV dP/dt(max) by dobutamine infusion (ALV dP/dt(max)). These are Group I (n=7) with ALV dP/dt(max) > 90%, and Group II (n=7) with ALV dP/dt(max) <90%. Out of 485 miRNAs, 32 were differentially expressed in the myocardium with reduced catecholarnine sensitivity. Among those, four miRNAs were decreased and one miRNA was increased in the Group II compared to the Group I (p <0.01). LVEF measured by left ventriculography at baseline did not differ between the 2 groups. Also there were no differences in plasma norepinephrine levels between the 2 groups.
Conclusions: Altered expression of several miRNAs was related to the reduced catecholamine sensitivity in mildly symptomatic patients with DCM. These findings shed light on the potential of miRNAs to provide possible etiologic insights as well as therapeutic targets for CHF.

• 出版日期2011-5