Introduction: New treatments are required to improve clinical outcomes in patients with acute myocardial infarction (AMI), for reduction of myocardial infarct (MI) size and preventing heart failure. Following AMI, acute ischemia/reperfusion injury (IRI) ensues, resulting in cardiomyocyte death and impaired cardiac function. Emerging studies have implicated a fundamental role for non-coding RNAs (microRNAs [miRNA], and more recently long non-coding RNAs [lncRNA]) in the setting of acute myocardial IRI.
Areas covered: In this article, we discuss the roles of miRNAs and lncRNAs as potential biomarkers and therapeutic targets for the detection and treatment of AMI, review their roles as mediators and effectors of cardioprotection, particularly in the settings of interventions such as ischemic pre- and post-conditioning (IPC & IPost) as well as remote ischemic conditioning (RIC), and highlight future strategies for targeting ncRNAs to reduce MI size and prevent heart failure following AMI.
Expert opinion: Investigating the roles of miRNAs and lncRNAs in the setting of AMI has provided new insights into the pathophysiology underlying acute myocardial IRI, and has identified novel biomarkers and therapeutic targets for detecting and treating AMI. Pharmacological and genetic manipulation of these ncRNAs has the therapeutic potential to improve clinical outcomes in AMI patients. 相似文献
Hospital volume and often also operator volume have documented impacts on the quality of care for aortic and aortocoronary bypass surgery, for percutaneous angioplasty and for radiofrequency ablation for arrhythmias, whereas data are less consistent for treatment of acute myocardial infarction. A review of this research is given. In the Nordic countries hospitals are small, and often the plateau of the learning curve cannot be reached. To discourage low-volume centers from embarking upon too complicated interventional or surgical procedures, the author suggests that a minimal number should be set for certain major procedures, both for hospitals and for physicians. 相似文献
Volatile anaesthetics emerged as important cardioprotective agents in both animal models of ischaemia/reperfusion injury and humans with coronary artery disease. Their administration before a prolonged ischaemic episode is known as anaesthetic preconditioning, whereas when given at the very onset of reperfusion, the strategy is termed anaesthetic postconditioning. Both types of anaesthetic conditioning reduce, albeit not to the same degree, the extent of myocardial injury. They share similar, albeit not identical, intracellular signal transduction pathways with their widely investigated counterparts, ischaemic pre‐ and postconditioning. Despite a wealth of preclinical evidence for cardioprotection for anaesthetic conditioning strategies, their translation into clinical therapy has been rather disappointing. This review highlights the major findings on the cardioprotective effects of volatile anaesthetics in experimental settings. It explores hypotheses that may explain the lack of efficacy observed in several past clinical studies paving the way for future preclinical and translational studies. 相似文献
Nicorandil is an anti-anginal agent that has been used in the United Kingdom for over 6 years and is becoming increasingly popular. It induces coronary and peripheral vasodilatation via a dualistic mode of action, mediated by the opening of potassium-ATP channels (KATP) and its nitrate effect by stimulation of adenyl cyclase, with an increase in cGMP levels. Comparison to nitrates and other anti-anginal agents have shown it to be of equal efficacy in relieving ischaemic symptoms. Recent evidence suggests a role for nicorandil as a myocardial preconditioning agent but this may be limited by systemic vasodilatation. There is ongoing research into its role in improving the long-term outcome of patients with ischaemic heart disease (IHD). It has been shown to be of proven efficacy in the treatment of IHD and further research will clarify other uses of this agent. 相似文献
Cardiovascular disease (CVD) is a major cause of death worldwide. Of the many etiological factors, microorganisms constitute one. From the local impact of the gut microbiota on energy metabolism and obesity, to the distal association of periodontal disease with coronary heart disease, microbes have a significant impact on cardiovascular health. In terms of the ability to modulate or influence the microbes, probiotic applications have been considered. These are live microorganisms which when administered in adequate amounts confer a benefit on the host. While a number of reports have established the beneficial abilities of certain probiotic bacterial strains to reduce cholesterol and hypertension, recent research suggests that their use could be more widely applied. This review presents an up-to-date summary of the known associations of the microbiome with CVD, and potential applications of probiotic therapy. 相似文献
Myocardium has the innate potential to adapt to transient sublethal ischaemia so that it becomes more resistant to a subsequent, more severe, ischaemic insult. The response is called ischaemic preconditioning and protection of the myocardium is manifested by a slowing of adenosine triphosphate decline, limitation of ischaemic necrosis and a reduction in dysrhythmia severity. Protection conferred by preconditioning occurs in two distinct temporal phases. An early phase of protection is observed immediately but wanes within two to three hours (classic preconditioning). This is followed many hours later by a second window of protection (delayed preconditioning). The cellular mechanisms underpinning both forms of protection are currently being intensively investigated. There is evidence that human myocardium can be preconditioned ex vivo and also in situ during elective procedures such as angioplasty and coronary artery bypass grafting. Furthermore, evidence points to the possibility that preconditioning occurs naturally in some ischaemic syndromes, particularly warm-up angina and preinfarction angina. Ultimately, investigation of the mechanisms of preconditioning may contribute to the development of rational therapies for protecting the ischaemic myocardium and, perhaps more importantly, enhance our understanding of the molecular basis of ischaemic heart disease. 相似文献
Background: In recent years, a number of companies, universities and other institutions have invested in research on new molecules acting as agonists, antagonists and enhancers on A1 adenosine receptors (ARs) and in the evaluation of their new therapeutic applications. Objective: To review recent patenting activity on this topic. Methods: The first part of this article describes the compounds patented, subdivided by functional activity, and the second part the most relevant therapeutic applications or new uses for A1 AR ligands, with a focus on compounds in or soon to be in clinical trials. Conclusion: Although a number of potential therapeutic applications are proposed in the recent literature, at present, in the authors' opinion, very few A1 ligands are close to coming on the market, probably due to limited selectivity towards the target tissue or organ. 相似文献
Melatonin confers cardioprotective effect against myocardial ischemia/reperfusion (MI/R) injury by reducing oxidative stress. Activation of silent information regulator 1 (SIRT1) signaling also reduces MI/R injury. We hypothesize that melatonin may protect against MI/R injury by activating SIRT1 signaling. This study investigated the protective effect of melatonin treatment on MI/R heart and elucidated its potential mechanisms. Rats were exposed to melatonin treatment in the presence or the absence of the melatonin receptor antagonist luzindole or SIRT1 inhibitor EX527 and then subjected to MI/R operation. Melatonin conferred a cardioprotective effect by improving postischemic cardiac function, decreasing infarct size, reducing apoptotic index, diminishing serum creatine kinase and lactate dehydrogenase release, upregulating SIRT1, Bcl‐2 expression and downregulating Bax, caspase‐3 and cleaved caspase‐3 expression. Melatonin treatment also resulted in reduced myocardium superoxide generation, gp91phox expression, malondialdehyde level, and increased myocardium superoxide dismutase (SOD) level, which indicate that the MI/R‐induced oxidative stress was significantly attenuated. However, these protective effects were blocked by EX527 or luzindole, indicating that SIRT1 signaling and melatonin receptor may be specifically involved in these effects. In summary, our results demonstrate that melatonin treatment attenuates MI/R injury by reducing oxidative stress damage via activation of SIRT1 signaling in a receptor‐dependent manner. 相似文献