University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom; School of Life and Health Sciences, Aston University, Birmingham, United Kingdom.
J Am Coll Cardiol. 2013 Oct 22;62(17):1541-51. doi: 10.1016/j.jacc.2013.07.043. Epub 2013 Aug 21.
Despite improvements in interventional and pharmacological therapy of atherosclerotic disease, it is still the leading cause of death in the developed world. Hence, there is a need for further development of effective therapeutic approaches. This requires better understanding of the molecular mechanisms and pathophysiology of the disease. Atherosclerosis has long been identified as having an inflammatory component contributing to its pathogenesis, whereas the available therapy primarily targets hyperlipidemia and prevention of thrombosis. Notwithstanding a pleotropic anti-inflammatory effect to some therapies, such as acetyl salicylic acid and the statins, none of the currently approved medicines for management of either stable or complicated atherosclerosis has inflammation as a primary target. Monocytes, as representatives of the innate immune system, play a major role in the initiation, propagation, and progression of atherosclerosis from a stable to an unstable state. Experimental data support a role of monocytes in acute coronary syndromes and in outcome post-infarction; however, limited research has been done in humans. Analysis of expression of various cell surface receptors allows characterization of the different monocyte subsets phenotypically, whereas downstream assessment of inflammatory pathways provides an insight into their activity. In this review we discuss the functional role of monocytes and their different subpopulations in atherosclerosis, acute coronary syndromes, cardiac healing, and recovery with an aim of critical evaluation of potential future therapeutic targets in atherosclerosis and its complications. We will also discuss technical difficulties of delineating different monocyte subpopulations, understanding their differentiation potential and function.
尽管动脉粥样硬化疾病的介入和药物治疗有所改善，但它仍然是发达国家的主要死亡原因。因此，需要进一步开发有效的治疗方法。这需要更好地了解疾病的分子机制和病理生理学。长期以来，动脉粥样硬化被认为具有炎症成分，有助于其发病机制，而现有治疗方法主要针对高脂血症和血栓形成的预防。尽管某些疗法（如乙酰水杨酸和他汀类药物）具有多效抗炎作用，但目前批准用于治疗稳定或复杂动脉粥样硬化的药物均未将炎症作为主要靶点。单核细胞作为先天免疫系统的代表，在动脉粥样硬化从稳定状态向不稳定状态的发生、发展和进展中起着重要作用。实验数据支持单核细胞在急性冠状动脉综合征和梗死后预后中的作用；然而，在人类中进行的研究有限。各种细胞表面受体的表达分析允许对不同的单核细胞亚群进行表型特征分析，而下游炎症途径的评估则提供了对其活性的深入了解。在这篇综述中，我们讨论了单核细胞及其在动脉粥样硬化、急性冠状动脉综合征、心脏愈合和恢复中的不同亚群的功能作用，旨在对动脉粥样硬化及其并发症的潜在未来治疗靶点进行批判性评估。我们还将讨论区分不同单核细胞亚群、理解其分化潜能和功能的技术困难。
