Research on microRNAs RegulatingResearch on microRNAs RegulatingCardiac ArrhythmiasCardiac Arrhythmias

艾 静 杨宝峰哈尔滨医科大学药理教研室

Department of Pharmacology, Harbin Medical UniversityState-Province Key Laboratories

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In China, about 3 million people died each year of

cardiovascular disease, approximately 45% of the total

mortality.

About 600,000 cardiogenic sudden death occurred each year,

more than 90% induced by malignant arrhythmias.

Harbin Medical University

Background

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Ischemia

Hypertrophy

Atrial fibrillationHeart failure

Arrhythmias

Arrhythmias is the common pathogenesis of heart diseases

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Antiarrhythmic drugs were not very efficient, the total

effective rate was only 30%-60%, and incidence of

proarrhythmic side effect >3%.

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Mechanisms

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Medicine Medicine

IKr/HERGIK1

IKr/HERG

1. Ion channelsK+ channel blockersCa2+ channel blockersNa+ channel blockers

InfarctionHealthyIK

ICaINa

Mechanisms of antiarrhythimic drugs

2. Receptorsβ-adrenoceptor blockers

3. Genes4. RAAS

MicroRNAs

Cell proliferation

Differentiation

Apoptosis

Metabolism

Stress

Development

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MicroRNAs and Arrhythmias

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Atrial fibrillation (AF)

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ECG recordings of sinus rhythm and AF

Electriac Remodeling

Structural Remodeling

Autonomomic Remodeling

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Atrial Remodeling Electriac Remodeling

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Atrial Remodeling- Electriac Remodeling

miR-26

KCNH2/Ikr

miR-1

EADs DADsNCX/Na+-Ca2+ exchanger

miR-27 miR-214 miR-30

HCN2/IfHCN4/If

miR-133

CACNA1C/Cav1.2CACNB1/Cavβ1

miR-328miR-133

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Atrial Remodeling- Structural Remodeling

miR-30miR-29miR-133mir-590

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Atrial Remodeling- Autonomomic Remodeling

Parasympathetic nervous systerm Sympathetic nervous systerm

IkAch

ICa(L)

KCNJ3/Kir3.1KCNJ5/Kir3.4

miR-30,miR-150

miR-1

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miR-328

miR-1, miR-26 miR-133, miR-590miR-29, miR-30

Electriac Remodeling

Structural Remodeling

Autonomomic Remodeling

FibrosisApoptosis

Ionic remodelingCa2+ - handling

MicroRNAs and AF

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Schematic summary of regulation of various genes pertinent to AF by miRNAs based on published studies

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Malignant ventricular arrhythmias

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Abnormal expression of miRNAs in hypertrophy and myocardial infarction

miR-499

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miRNAs regulate target genes in APD

SCN5A/INa

miR-1miR-195

KCND2/ItoKCND3/Ito

miR-1,miR-133

KCNQ1/IksKCNE1/Iks

miR-133miR-1

KCNJ2/Ik1 miR-1miR-26

KCNH2(HERG)/IkrKCNE2/Ikr

miR-133

miR-1

miR-133miR-328

CACNA1C/Cav1.2

CACNB1/Cavβ1

KCNJ2/Ik1 miR-1

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不同的 microRNAs 调节一个靶基因发挥作用 ;

一个 microRNAs 调节多个靶基因发挥作用。

MicroRNAs 通过调节 APD 过程中不同通道蛋白参与心律失常的发生。

调节方式：

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Arrhythmias (Sudden death)Harbin Medical University

Myocardial Infarction

miR-1

Role of miRNA-1 in malignant Arrhythmias

conduction

GJA1/Cx43/Ij

repolarization

KCNJ2/Kir2.1/IK1

Ik1

Ca2+ handling

B56a/RyR2

SR

Hsp60, Hsp70

Apoptosisstructure

cMLCK/CaM

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MicroRNA-1 通过调节不同的生物学过程参与心律失常的发生和发展过程。

miR-1

miR-133

miR-328miR-26

miR-30miR-499

miR-21

miR-195miR-181

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Arrhythmias (Sudden death)

conduction repolarization structure Ca2+ handling dispersion fibrosis

Harbin Medical University

Myocardial Infarction

Atrial FibrosisHyperlipidemia

Hypertrophy Heart Failure

DiabeticCardiomyopathy

miR-1

GJA1/Cx43/Ij

KCNH2/ERG/IKrKCNJ2/Kir2.1/IK1

miR-133/590miR-328

TGF-βsignalingcMLCK/CaM

Cav1.2/ICa

miR-26

CACNAB1/Cavβ1Calcineurin

Summary of role of miRNAs in malignant heart diseases

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Autonomic nervous systerm regulation of heart function

microRNAs

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M3R↑ miR-1↓ Kir2.1/IK1↑ RMP

VT↓

Sudden death↓

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Harbin Medical University

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Harbin Medical University

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Harbin Medical University

Lab members

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