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

Hidehito Funahashi, Hideo Izawa, Akihiro Hirashiki, Xian Wu Cheng, Yasuya Inden, Masanori Nomura, Toyoaki Murohara

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)338-344
Number of pages7
JournalJournal of cardiology
Volume57
Issue number3
DOIs
Publication statusPublished - 01-05-2011

Fingerprint

MicroRNAs
Catecholamines
Heart Failure
Dobutamine
Dilated Cardiomyopathy
Small Untranslated RNA
Ventricular Pressure
Regulator Genes
Microarray Analysis
Myocardium
Norepinephrine
Biopsy

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Funahashi, Hidehito ; Izawa, Hideo ; Hirashiki, Akihiro ; Cheng, Xian Wu ; Inden, Yasuya ; Nomura, Masanori ; Murohara, Toyoaki. / Altered microRNA expression associated with reduced catecholamine sensitivity in patients with chronic heart failure. In: Journal of cardiology. 2011 ; Vol. 57, No. 3. pp. 338-344.
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abstract = "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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Altered microRNA expression associated with reduced catecholamine sensitivity in patients with chronic heart failure. / Funahashi, Hidehito; Izawa, Hideo; Hirashiki, Akihiro; Cheng, Xian Wu; Inden, Yasuya; Nomura, Masanori; Murohara, Toyoaki.

In: Journal of cardiology, Vol. 57, No. 3, 01.05.2011, p. 338-344.

Research output: Contribution to journalArticle

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AU - Nomura, Masanori

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