Bristol Heart Institute and Translational Biomedical Research Centre, Faculty of Health Science, University of Bristol, Bristol, UK.
Bristol Heart Institute and Translational Biomedical Research Centre, Faculty of Health Science, University of Bristol, Bristol, UK.
Pharmacol Ther. 2023 May;245:108397. doi: 10.1016/j.pharmthera.2023.108397. Epub 2023 Mar 28.
Myocardial healing following myocardial infarction (MI) toward either functional tissue repair or excessive scarring/heart failure, may depend on a complex interplay between nervous and immune system responses, myocardial ischemia/reperfusion injury factors, as well as genetic and epidemiological factors. Hence, enhancing cardiac repair post MI may require a more patient-specific approach targeting this complex interplay and not just the heart, bearing in mind that the dysregulation or modulation of just one of these systems or some of their mechanisms may determine the outcome either toward functional repair or toward heart failure. In this review we have elected to focus on existing preclinical and clinical in-vivo studies aimed at testing novel therapeutic approaches targeting the nervous and immune systems to trigger myocardial healing toward functional tissue repair. To this end, we have only selected clinical and preclinical in-vivo studies reporting on novel treatments targeting neuro-immune systems to ultimately treat MI. Next, we have grouped and reported treatments under each neuro-immune system. Finally, for each treatment we have assessed and reported the results of each clinical/preclinical study and then discussed their results collectively. This structured approach has been followed for each treatment discussed. To keep this review focused, we have deliberately omitted to cover other important and related research areas such as myocardial ischemia/reperfusion injury, cell and gene therapies as well as any ex-vivo and in-vitro studies. The review indicates that some of the treatments targeting the neuro-immune/inflammatory systems appear to induce beneficial effects remotely on the healing heart post MI, warranting further validation. These remote effects on the heart also indicates the presence of an overarching synergic response occurring across the nervous and immune systems in response to acute MI, which appear to influence cardiac tissue repair in different ways depending on age and timing of treatment delivery following MI. The cumulative evidence arising from this review allows also to make informed considerations on safe as opposed to detrimental treatments, and within the safe treatments to ascertain those associated with conflicting or supporting preclinical data, and those warranting further validation.
心肌梗死后（MI）心肌的修复方向是功能性组织修复还是过度瘢痕/心力衰竭，可能取决于神经系统和免疫系统反应、心肌缺血/再灌注损伤因素以及遗传和流行病学因素之间的复杂相互作用。因此，增强 MI 后心脏修复可能需要一种更针对这种复杂相互作用的个体化方法，而不仅仅是针对心脏，因为这些系统中的一个或其中一些机制的失调或调节可能会决定修复方向是朝向功能性修复还是心力衰竭。在这篇综述中，我们选择关注旨在测试针对神经系统和免疫系统的新型治疗方法的现有临床前和体内临床研究，以触发向功能性组织修复的心肌愈合。为此，我们仅选择了报告针对神经-免疫系统的新型治疗方法以最终治疗 MI 的临床前和体内临床研究。接下来，我们根据每个神经-免疫系统对治疗方法进行分组和报告。最后，对于每种治疗方法，我们评估并报告了每项临床/临床前研究的结果，然后集体讨论了它们的结果。我们遵循了这种结构化的方法来讨论每种治疗方法。为了使本综述重点突出，我们故意省略了涵盖其他重要且相关的研究领域，如心肌缺血/再灌注损伤、细胞和基因治疗以及任何离体和体外研究。该综述表明，一些针对神经-免疫/炎症系统的治疗方法似乎在 MI 后对愈合的心脏产生有益的远程影响，这需要进一步验证。这些对心脏的远程影响也表明，在急性 MI 后，神经系统和免疫系统之间存在一种广泛的协同反应，这种反应似乎以不同的方式影响心脏组织修复，这取决于治疗的年龄和 MI 后治疗的时间。本综述得出的综合证据还允许对安全治疗与有害治疗进行明智的考虑，并在安全治疗中确定那些与相互矛盾或支持的临床前数据相关的治疗方法，以及那些需要进一步验证的治疗方法。
