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miRNAs at the heart of the matter.

Wang Z, Luo X, Lu Y, Yang B - J. Mol. Med. (2008)

Bottom Line: The target genes and signaling pathways linking the miRNAs to cardiovascular disease are highlighted.The applications of miRNA interference technologies for manipulating miRNA expression, stability, and function as new strategies for molecular therapy of human disease are evaluated.Finally, some specific issues related to future directions of the research on miRNAs relevant to cardiovascular disease are pinpointed and speculated.

View Article: PubMed Central - PubMed

Affiliation: Research Center, Montreal Heart Institute, Montreal, PQ H1T 1C8, Canada. wz.email@gmail.com

ABSTRACT
Cardiovascular disease is among the main causes of morbidity and mortality in developed countries. The pathological process of the heart is associated with altered expression profile of genes that are important for cardiac function. MicroRNAs (miRNAs) have emerged as one of the central players of gene expression regulation. The implications of miRNAs in the pathological process of cardiovascular system have recently been recognized, representing the most rapidly evolving research field. Here, we summarize and analyze the currently available data from our own laboratory and other groups, providing a comprehensive overview of miRNA function in the heart, including a brief introduction of miRNA biology, expression profile of miRNAs in cardiac tissue, role of miRNAs in cardiac hypertrophy and heart failure, the arrhythmogenic potential of miRNAs, the involvement of miRNAs in vascular angiogenesis, and regulation of cardiomyocyte apoptosis by miRNAs. The target genes and signaling pathways linking the miRNAs to cardiovascular disease are highlighted. The applications of miRNA interference technologies for manipulating miRNA expression, stability, and function as new strategies for molecular therapy of human disease are evaluated. Finally, some specific issues related to future directions of the research on miRNAs relevant to cardiovascular disease are pinpointed and speculated.

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Related in: MedlinePlus

Schematic illustration of the role of the muscle-specific miRNAs miR-1 and miR-133 in arrhythmias. Cx43 connexin-43; IK1 inward rectifier K+ current; IKr rapid delayed rectifier K+ current; IKs slow delayed rectifier K+ current; If pacemaker nonselective cation current or funny current; Kir2.1 a pore-forming K+ channel α-subunit for IK1; HERG a pore-forming K+ channel α-subunit for IKr; KCNQ1 a pore-forming K+ channel α-subunit for IKs; KCNE1 an auxiliary β-subunit for IKs; HCN2 and HCN4 α-subunits for If; APD action potential duration; ERP effective refractory period; EAD early after depolarization
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Fig2: Schematic illustration of the role of the muscle-specific miRNAs miR-1 and miR-133 in arrhythmias. Cx43 connexin-43; IK1 inward rectifier K+ current; IKr rapid delayed rectifier K+ current; IKs slow delayed rectifier K+ current; If pacemaker nonselective cation current or funny current; Kir2.1 a pore-forming K+ channel α-subunit for IK1; HERG a pore-forming K+ channel α-subunit for IKr; KCNQ1 a pore-forming K+ channel α-subunit for IKs; KCNE1 an auxiliary β-subunit for IKs; HCN2 and HCN4 α-subunits for If; APD action potential duration; ERP effective refractory period; EAD early after depolarization

Mentions: Arrhythmias are electrical disturbances that can result in irregular heart beating with consequent insufficient pumping of blood. Arrhythmias are often lethal, constituting a major cause for cardiac death in myocardial infarction and heart failure and being one of the most difficult clinical problems [44]. Arrhythmias can occur when there is abnormality in the electrical activities: cardiac conduction, repolarization, or automaticity. The electrical activities of the heart are determined by ion channels, the transmembrane proteins embedded across the cytoplasmic membrane of cardiomyocytes. Sodium channels and connexin43 (Cx43) are responsible for excitation generation and intercell conduction of excitations, respectively. Calcium channels account for excitation–contraction coupling and also contribute to pacemaker activities. Potassium channels govern the membrane potential and rate of membrane repolarization. Pacemaker channels, which carry the nonselective cation currents, are critical in generating sinus rhythm and ectopic heart beats as well. Intricate interplays of these ion channels maintain the normal heart rhythm. Dysfunction of any of the ion channels can render arrhythmias (Fig. 2).Fig. 2


miRNAs at the heart of the matter.

Wang Z, Luo X, Lu Y, Yang B - J. Mol. Med. (2008)

Schematic illustration of the role of the muscle-specific miRNAs miR-1 and miR-133 in arrhythmias. Cx43 connexin-43; IK1 inward rectifier K+ current; IKr rapid delayed rectifier K+ current; IKs slow delayed rectifier K+ current; If pacemaker nonselective cation current or funny current; Kir2.1 a pore-forming K+ channel α-subunit for IK1; HERG a pore-forming K+ channel α-subunit for IKr; KCNQ1 a pore-forming K+ channel α-subunit for IKs; KCNE1 an auxiliary β-subunit for IKs; HCN2 and HCN4 α-subunits for If; APD action potential duration; ERP effective refractory period; EAD early after depolarization
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2480593&req=5

Fig2: Schematic illustration of the role of the muscle-specific miRNAs miR-1 and miR-133 in arrhythmias. Cx43 connexin-43; IK1 inward rectifier K+ current; IKr rapid delayed rectifier K+ current; IKs slow delayed rectifier K+ current; If pacemaker nonselective cation current or funny current; Kir2.1 a pore-forming K+ channel α-subunit for IK1; HERG a pore-forming K+ channel α-subunit for IKr; KCNQ1 a pore-forming K+ channel α-subunit for IKs; KCNE1 an auxiliary β-subunit for IKs; HCN2 and HCN4 α-subunits for If; APD action potential duration; ERP effective refractory period; EAD early after depolarization
Mentions: Arrhythmias are electrical disturbances that can result in irregular heart beating with consequent insufficient pumping of blood. Arrhythmias are often lethal, constituting a major cause for cardiac death in myocardial infarction and heart failure and being one of the most difficult clinical problems [44]. Arrhythmias can occur when there is abnormality in the electrical activities: cardiac conduction, repolarization, or automaticity. The electrical activities of the heart are determined by ion channels, the transmembrane proteins embedded across the cytoplasmic membrane of cardiomyocytes. Sodium channels and connexin43 (Cx43) are responsible for excitation generation and intercell conduction of excitations, respectively. Calcium channels account for excitation–contraction coupling and also contribute to pacemaker activities. Potassium channels govern the membrane potential and rate of membrane repolarization. Pacemaker channels, which carry the nonselective cation currents, are critical in generating sinus rhythm and ectopic heart beats as well. Intricate interplays of these ion channels maintain the normal heart rhythm. Dysfunction of any of the ion channels can render arrhythmias (Fig. 2).Fig. 2

Bottom Line: The target genes and signaling pathways linking the miRNAs to cardiovascular disease are highlighted.The applications of miRNA interference technologies for manipulating miRNA expression, stability, and function as new strategies for molecular therapy of human disease are evaluated.Finally, some specific issues related to future directions of the research on miRNAs relevant to cardiovascular disease are pinpointed and speculated.

View Article: PubMed Central - PubMed

Affiliation: Research Center, Montreal Heart Institute, Montreal, PQ H1T 1C8, Canada. wz.email@gmail.com

ABSTRACT
Cardiovascular disease is among the main causes of morbidity and mortality in developed countries. The pathological process of the heart is associated with altered expression profile of genes that are important for cardiac function. MicroRNAs (miRNAs) have emerged as one of the central players of gene expression regulation. The implications of miRNAs in the pathological process of cardiovascular system have recently been recognized, representing the most rapidly evolving research field. Here, we summarize and analyze the currently available data from our own laboratory and other groups, providing a comprehensive overview of miRNA function in the heart, including a brief introduction of miRNA biology, expression profile of miRNAs in cardiac tissue, role of miRNAs in cardiac hypertrophy and heart failure, the arrhythmogenic potential of miRNAs, the involvement of miRNAs in vascular angiogenesis, and regulation of cardiomyocyte apoptosis by miRNAs. The target genes and signaling pathways linking the miRNAs to cardiovascular disease are highlighted. The applications of miRNA interference technologies for manipulating miRNA expression, stability, and function as new strategies for molecular therapy of human disease are evaluated. Finally, some specific issues related to future directions of the research on miRNAs relevant to cardiovascular disease are pinpointed and speculated.

Show MeSH
Related in: MedlinePlus