“Second-generation” stem cells for cardiac repair

Over the last years, stem cell therapy has emerged asan inspiring alternative to restore cardiac function after myocardial infarction. A large body of evidence has been obtained in this field but there is no conclusive data on the efficacy of these treatments. Preclinical studies and early reports in humans have been encouraging and have fostered a rapid clinical translation, but positive results have not been uniformly observed and when present, they have been modest. Several types of stem cells, manufacturing methods and delivery routes have been tested in different clinical settings but direct comparison between them is challenging and hinders further research. Despite enormous achievements, major barriers have been found and many fundamental issues remain to be resolved. A better knowledge of the molecular mechanisms implicated in cardiac development and myocardial regeneration is critically needed to overcome some of these hurdles. Genetic and pharmacological priming together with the discovery of new sources of cells have led to a "second generation" of cell products that holds an encouraging promise in cardiovascular regenerative medicine. In this report, we review recent advances in this field focusing on the new types of stem cells that are currently being tested in human beings and on the novel strategies employed to boost cell performance in order to improve cardiac function and outcomes after myocardial infarction.

Contemporary perspective on endogenous myocardial regeneration

Considering the complex nature of the adult heart, it is no wonder that innate regenerative processes, while maintaining adequate cardiac function, fall short in myocardial jeopardy. In spite of these enchaininglimitations, cardiac rejuvenation occurs as well as restricted regeneration. In this review, the background as well as potential mechanisms of endogenous myocardial regeneration are summarized. We present and analyze the available evidence in three subsequent steps. First, we examine the experimental research data that provide insights into the mechanisms and origins of the replicating cardiac myocytes, including cell populations referred to as cardiac progenitor cells(i.e., c-kit+ cells). Second, we describe the role of clinical settings such as acute or chronic myocardial ischemia, as initiators of pathways of endogenous myocardial regeneration. Third, the hitherto conducted clinical studies that examined different approaches of initiating endogenous myocardial regeneration in failing human hearts are analyzed. In conclusion, we present the evidence in support of the notion that regaining cardiac function beyond cellular replacement of dysfunctional myocardium via initiation of innate regenerative pathways could create a new perspective and a paradigm change in heart failure therapeutics. Reinitiating cardiac morphogenesis by reintroducing developmental pathways in the adult failing heart might provide a feasible way of tissue regeneration. Based on our hypothesis "embryonic recall", we present first supporting evidence on regenerative impulses in the myocardium, as induced by developmental processes.

Early reperfusion strategy for acute myocardial infarction:a need for clinical implementation

Reperfusion is the key strategy in acute ST-segment elevation myocardial infarction (STEMI) care,and it is time-dependent.Shortening the time from symptom to reperfusion and choosing the optimal reperfusion strategy for STEMI patients are great challenges in practice.We need to improve upon the problems of low reperfusion rate,non-standardized treatment,and economic burden in STEMI care.This article briefly reviews the current status of reperfusion strategy in STEMI care,and also introduces what we will do to bridge the gap between the guidelines and implementation in the clinical setting through the upcoming China STEMI early reperfusion program.

Differential gene expression profile of Buyanghuanwu decoction in rats with ventricular remodeling post-myocardial infarction

OBJECTIVE: To investigate the effect of Buyanghuanwu decoction(BYHWD) on gene expression in ventricular remodeling post-myocardial infarction in rats.METHODS: Animal models of myocardial infarction were established by permanent ligation of the left anterior descending coronary artery. Echocardiography measurements were performed after the treatment of BYHWD(18 g·kg-1 collagen was observ·d-1) for 90 days.Myocardialed by mallory trichrome staining. Capillary density was quantified by using Factor rentially expⅧre immunohistochemical staining.Diffessed genes were explored by a short-read sequencing technology combined with a tag-based digital gene expression profiling(DGE)system. Real-time quantitative polymerase chain reaction detecting system(q PCR) was used to validate the sequencing results. After assembling the gene information from Sham, model and BYHWD groups, we constructed three DGE libraries based on each group. The sequencing of three libraries generated 66 000-73 000 unique tags, which were mapped to reference sequences for annotation of expressed genes.RESULTS: Among them, 511 and 352 differentially expressed genes were found in comparison with sham/model and model/BYHWD, respectively. Fifty-five genes exhibited reversed direction of gene expression differences between Sham/Model and Model/BYHWD groups. We found that transforming growth factor beta receptor-1, junctophilin-2,monocyte chemotactic protein 1, neuropeptide Y,arachidonate 5-Lipoxygenase, arachidonate 15-Lipoxygenase were significantly modulated, which suggested the involvement of these genes in BYHWD treatment.CONCLUSION: The DGE profiling data provide comprehensive gene expression information at the transcriptional level that could facilitate our understanding of the pharmacological mechanisms of BYHWD in ventricular remodeling post-myocardial infarction.

The prognostic role of N-terminal prohormone brain natriuretic peptide and TIMI risk score in patients with ST segment elevation myocardial infarction

Background ST segment elevation myocardial infarction （STEMI） remains a major cause of death world-wide. The thrombolysis in myocardial infarction （TIMI） risk score is a risk assessment tool to detect high risk STEMI patients. NT-proBNP has been used to assess the severity of heart failure. However, the predictive power of TIMI risk score is not high enough to identify all high-risk patients, and whether NT-proBNP adds power to the TIMI risk score for predicting in-hospital mortality is unclear. Methods 664 STEMI patients were included and divided into 3 groups according to TIMI risk score ≤3 （n=211）, 4-6 （n=281）, and ≥7 （n=172）. The relation-ships between TIM! risk score and events were evaluated. The modified TIMI risk score was constructed through multivariate logistic regression analysis. Results The proportion of in-hospital death （0.5% vs. 3.2% vs. 10.5%, P〈0.001） and major adverse clinical events （MACEs） （14.2% vs. 22.8% vs. 40.1%, P〈0.001） increased as higher TIMI risk score was. ROC curve showed that the AUC of NT-proBNP for predicting in-hospital death was 0.792, with optimal cut-off being 3500pg/mL. Multivariate logistic regression analysis revealed that TIMI risk score （OR=1.26, 95% CI 1.05-1.50, P=0.012） and NT-proBNP〉3500pg/mL （OR=7.30, 95% CI 2.56-20.83, P〈0.001） were independently associated with in-hospital death. Adding NT-proBNP to TIMI risk score produced higher predictive value （AUC： 0.871 vs. 0.804, P=0.040）. Conclusion NT-proBNP is associated with in-hospital death in STEMI patients and has an additive prognostic value to TIMI risk score.