Myocardial protection in man—from research concept to clinical practice

Cokkinos, Dennis V.; Pantos, Costas

doi:10.1007/s10741-007-9030-5

Cited by 23 publications

(12 citation statements)

References 209 publications

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“…About 3 million people die from CHD every year and now an estimated 2 million people have AMI in China. In recent years, the survival of AMI patients has improved with better therapeutic strategies such as percutaneous coronary intervention and coronary artery bypass graft [2]. However, the absolute number of deaths has remained almost constant because of an increase in the size of the population and the proportion of older people [3].…”

Section: Introductionmentioning

confidence: 99%

Serum microRNAs profile from genome-wide serves as a fingerprint for diagnosis of acute myocardial infarction and angina pectoris

Fang

Jiang

et al. 2013

BMC Med Genomics

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BackgroundIn order to identify miRNAs expression profiling from genome-wide screen for diagnosis of acute myocardial infarction (AMI) and angina pectoris (AP), we investigated the altered profile of serum microRNAs in AMI and AP patients at a relative early stage.MethodsSerum samples were taken from 117 AMI patients, 182 AP patients and 100 age-and gender-matched controls. An initial screening of miRNAs expression was performed by Solexa sequencing. Differential expression was validated using RT-qPCR in individuals samples, the samples were arranged in a two-phase selection and validation.ResultsThe Solexa sequencing results demonstrated marked upregulation of serum miRNAs in AMI patients compared with controls. RT-qPCR analysis identified a profile of six serum miRNAs (miR-1, miR-134, miR-186, miR-208, miR-223 and miR-499) as AMI biomarkers. MiR-208 and miR-499 were elevated higher in AP cases than in AMI cases. The ROC curves indicated a panel of six miRNAs has a great potential to offer sensitive and specific diagnostic tests for AMI. More especially, the panel of six miRNAs presents significantly differences between the AMI and AP cases.ConclusionsThe six-miRNAs signature identified from genome-wide serum miRNA expression profiling may serves as a fingerprint for AMI and AP diagnosis.

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Section: Introductionmentioning

confidence: 99%

Serum microRNAs profile from genome-wide serves as a fingerprint for diagnosis of acute myocardial infarction and angina pectoris

Fang

Jiang

et al. 2013

BMC Med Genomics

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“…Both percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) are effective for myocardial infarction (MI) [1]. However, ischemia reperfusion (IR) induced by revascularization may contribute to subsequent myocardial injury, in which apoptosis may play a key role in myocardial IR injury [2].…”

Section: Introductionmentioning

confidence: 99%

Role of miR-1 and miR-133a in myocardial ischemic postconditioning

et al. 2011

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BackgroundIschemic postconditioning (IPost) has aroused much attention since 2003 when it was firstly reported. The role of microRNAs (miRNAs or miRs) in IPost has rarely been reported. The present study was undertaken to investigate whether miRNAs were involved in the protective effect of IPost against myocardial ischemia-reperfusion (IR) injury and the probable mechanisms involved.MethodsThirty SD rats weighing 250-300 g were equally randomized to three groups: Control group, where the rats were treated with thoracotomy only; IR group, where the rats were treated with ischemia for 60 min and reperfusion for 180 min; and IPost group, where the rats were treated with 3 cycles of transient IR just before reperfusion. The extent of myocardial infarction, LDH and CK activities were measured immediately after treatment. Myocardial apoptosis was detected by TUNEL assay. The myocardial tissue was collected after IR or IPost stimulation to evaluate the miRNAs expression level by miRNA-microarray and quantitative real-time RT-PCR. Real-time PCR was conducted to identify changes in mRNA expression of apoptosis-related genes such as Bcl-2, Bax and Caspase-9 (CASP9), and Western blot was used to compare the protein expression level of CASP9 in the three groups. The miRNA mimics and anti-miRNA oligonucleotides (AMO) were transferred into the cultured neonatal cardiomyocytes and myocardium before they were treated with IR. The effect of miRNAs on apoptosis was determined by flow cytometry and TUNEL assay. CASP9, as one of the candidate target of miR-133a, was compared during IR after the miR-133a mimic or AMO-133a was transferred into the myocardium.ResultsIPost reduced the IR-induced infarct size of the left ventricle, and decreased CK and LDH levels. TUNEL assay showed that myocardial apoptosis was attenuated by IPost compared with IR. MiRNA-microarray and RT-PCR showed that myocardial-specific miR-1 and miR-133a were down-regulated by IR, and up-regulated by IPost compared with IR. Furthermore, IPost up-regulated the mRNA expression of Bcl-2, down-regulated that of Bax and CASP9. Western blot showed that IPost also down-regulated the CASP9 protein expression compared with IR. The results of flow cytometry and TUNEL assay showed that up-regulation of miR-1 and miR-133a decreased apoptosis of cardiomyocytes. MiR-133a mimic down-regulated CASP9 protein expression and attenuated IR-induced apoptosis.ConclusionMiRNAs are associated with the protective effect of IPost against myocardial IR injury. IPost can up-regulate miR-1 and miR-133a, and decrease apoptosis of cardiomyocyte. Myocardial-specific miR-1 and miR-133a may play an important role in IPost protection by regulating apoptosis-related genes. MiR-133a may attenuate apoptosis of myocardiocytes by targeting CASP9.

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“…Both human autopsy data and evidence from rodent models of MI indicate that most cell death happens by apoptosis during the initial 2–4 h following coronary occlusion 2,3. Clinical treatment of MI by thrombolytic therapy and revascularization by percutaneous coronary intervention or coronary artery bypass graft surgery are effective 1, 3. However, given the health, economic, and personal burden caused by ischemic heart disease, research into additional treatment modalities is imperative.…”

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confidence: 99%

MicroRNA-320 Is Involved in the Regulation of Cardiac Ischemia/Reperfusion Injury by Targeting Heat-Shock Protein 20

et al. 2009

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Background-Recent studies have identified critical roles for microRNAs (miRNAs) in a variety of cellular processes, including regulation of cardiomyocyte death. However, the signature of miRNA expression and possible roles of miRNA in the ischemic heart have been less well studied. Methods and Results-We performed miRNA arrays to detect the expression pattern of miRNAs in murine hearts subjected to ischemia/reperfusion (I/R) in vivo and ex vivo. Surprisingly, we found that only miR-320 expression was significantly decreased in the hearts on I/R in vivo and ex vivo. This was further confirmed by TaqMan real-time polymerase chain reaction. Gain-of-function and loss-of-function approaches were employed in cultured adult rat cardiomyocytes to investigate the functional roles of miR-320. Overexpression of miR-320 enhanced cardiomyocyte death and apoptosis, whereas knockdown was cytoprotective, on simulated I/R. Furthermore, transgenic mice with cardiac-specific overexpression of miR-320 revealed an increased extent of apoptosis and infarction size in the hearts on I/R in vivo and ex vivo relative to the wild-type controls. Conversely, in vivo treatment with antagomir-320 reduced infarction size relative to the administration of mutant antagomir-320 and saline controls. Using TargetScan software and proteomic analysis, we identified heat-shock protein 20 (Hsp20), a known cardioprotective protein, as an important candidate target for miR-320. This was validated experimentally by utilizing a luciferase/GFP reporter activity assay and examining the expression of Hsp20 on miR-320 overexpression and knockdown in cardiomyocytes. Conclusions-Our data demonstrate that miR-320 is involved in the regulation of I/R-induced cardiac injury and dysfunction via antithetical regulation of Hsp20. Thus, miR-320 may constitute a new therapeutic target for ischemic heart diseases. Key Words: apoptosis Ⅲ ischemia Ⅲ microRNA Ⅲ myocardial infarction Ⅲ reperfusion M ore than 1 million Americans suffer from myocardial infarction every year. 1 Both human autopsy data and evidence from rodent models of myocardial infarction indicate that most cell death happens by apoptosis during the initial 2 to 4 hours after coronary occlusion. 2,3 Clinical treatment of myocardial infarction by thrombolytic therapy and revascularization by percutaneous coronary intervention or coronary artery bypass graft surgery are effective. 1,3 However, given the health, economic, and personal burden caused by ischemic heart disease, research into additional treatment modalities is imperative. Furthermore, the molecular mechanisms that regulate gene expression during myocardial ischemia/reperfusion (I/R) are still not completely understood. Clinical Perspective on p 2366MicroRNAs (miRNAs) are a class of endogenous nonprotein-coding RNAs comprising Ϸ22 nucleotides. 4 -6 They regulate gene expression via RNA-induced silencing complexes, targeting them to mRNAs where they inhibit translation or direct destructive cleavage. 4 -6 Increasing evidence indicates the importa...

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Myocardial protection in man—from research concept to clinical practice

Cited by 23 publications

References 209 publications

Serum microRNAs profile from genome-wide serves as a fingerprint for diagnosis of acute myocardial infarction and angina pectoris

Serum microRNAs profile from genome-wide serves as a fingerprint for diagnosis of acute myocardial infarction and angina pectoris

Role of miR-1 and miR-133a in myocardial ischemic postconditioning

MicroRNA-320 Is Involved in the Regulation of Cardiac Ischemia/Reperfusion Injury by Targeting Heat-Shock Protein 20

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