TY - JOUR
T1 - Altered microRNA expression associated with reduced catecholamine sensitivity in patients with chronic heart failure
AU - Funahashi, Hidehito
AU - Izawa, Hideo
AU - Hirashiki, Akihiro
AU - Cheng, Xian Wu
AU - Inden, Yasuya
AU - Nomura, Masanori
AU - Murohara, Toyoaki
N1 - Funding Information:
This work was supported in part by Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Tokyo, Japan) (#19590808, #21590914 to H.I. and #18390232, #19659201, #20249045 to T.M.).
PY - 2011/5
Y1 - 2011/5
N2 - 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/dtmax) at baseline and during infusion of dobutamine (10μgkg-1min-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/dtmax by dobutamine infusion (ΔLV dP/dtmax). These are Group I (n=7) with ΔLV dP/dtmax>90%, and Group II (n=7) with ΔLV dP/dtmax<90%. Out of 485 miRNAs, 32 were differentially expressed in the myocardium with reduced catecholamine 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.
AB - 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/dtmax) at baseline and during infusion of dobutamine (10μgkg-1min-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/dtmax by dobutamine infusion (ΔLV dP/dtmax). These are Group I (n=7) with ΔLV dP/dtmax>90%, and Group II (n=7) with ΔLV dP/dtmax<90%. Out of 485 miRNAs, 32 were differentially expressed in the myocardium with reduced catecholamine 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.
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U2 - 10.1016/j.jjcc.2011.01.009
DO - 10.1016/j.jjcc.2011.01.009
M3 - Article
C2 - 21367584
AN - SCOPUS:79954994380
SN - 0914-5087
VL - 57
SP - 338
EP - 344
JO - Journal of cardiology
JF - Journal of cardiology
IS - 3
ER -