Monocytes: protagonists of infarct inflammation and repair after myocardial infarction.
Monocytes: protagonists of infarct inflammation and repair after myocardial infarction.
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DOI：
10.1161/circulationaha.109.916346
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发表时间：
2010-06-08
期刊：
影响因子：
37.8
通讯作者：
Swirski FK
中科院分区：
文献类型：
--
作者：
Nahrendorf M;Pittet MJ;Swirski FK
心肌梗死（MI）是心力衰竭的最常见原因，心力衰竭是一种致残性疾病，患病率高，社会经济影响广泛。2008年，美国有570万人患有心力衰竭，超过28.7万人死亡。1缺血心肌的及时血运重建可降低急性梗死死亡率，目前使用阻滞剂和血管紧张素转换酶（ACE）抑制剂的标准治疗可抑制MI后心力衰竭的发展。例如，ACE抑制剂治疗在存活和心室扩张（SAVE）试验中将死亡率从25%降低到20%。虽然这是一个重大进步，但长期死亡率仍然很高。由于有效的急性护理而降低的急性梗死死亡率和长期治疗梗死幸存者的选择不足，导致心力衰竭患病率增加（图1）。更好地理解和治疗心力衰竭的需要促使临床医生和基础科学家探索新的治疗策略来修复衰竭的心脏，例如，用干细胞。4，5 MI后1 - 2周内发生的内在伤口愈合增强是一种具有预防心力衰竭潜力的前瞻性方法。在此期间，梗塞是高度活跃的生物学。6-8精致的肉芽组织经历细胞和结构成分如细胞外基质的快速周转。先前存在的胶原蛋白被消化并形成新的基质。在组织结构的这些广泛变化期间，脆弱的伤口暴露于循环心室内压和心肌收缩的机械应力，并且心脏可以经历心室几何形状和功能的深刻和有害的变化。在短期内（数天、数周），愈合不良可导致梗死扩大和左心室扩张，在某些情况下可导致梗死破裂和死亡。长期（数月、数年），充盈压、室壁应力和左心室容积可增加并传播不良重构，导致心力衰竭和预后不良。7，9，10相反，“充分”愈合可保留左心室几何形状并预防心力衰竭。在这篇综述中，我们提出，损伤后不久梗死愈合的质量决定了患者未来几年的命运。
Myocardial infarction (MI) is the most frequent cause of heart failure, which is an incapacitating disease with high prevalence and broad socioeconomic impact. In 2008 in the United States, 5.7 million people suffered from heart failure, and more than 287 000 people died. 1 Timely revascularization of ischemic myocardium reduces acute infarct mortality, and current standard therapy with blockers and angiotensin-converting enzyme (ACE) inhibitors curbs development of post-MI heart failure. For example, ACE inhibitor treatment reduced mortality from 25% to 20% in the Survival and Ventricular Enlargement (SAVE) trial. 2 Although this is a major advance, long-term mortality remains high. The combination of reduced acute infarct mortality due to efficient acute care and insufficient options to treat infarct survivors chronically has contributed to an increased heart failure prevalence (Figure 1). 3 The need to understand and treat heart failure better has motivated clinicians and basic scientists to explore new therapeutic strategies to repair the failing heart, for instance, with stem cells. 4, 5 Augmentation of intrinsic wound healing that occurs during the first 1 to 2 weeks after MI is a prospective approach with the potential to prevent heart failure. During this period, the infarct is highly active biologically. 6–8 Delicate granulation tissue undergoes rapid turnover of cells and of structural components such as the extracellular matrix. Preexisting collagen is digested and new matrix is laid down. During these extensive changes of tissue architecture, the vulnerable wound is exposed to the mechanical stress of cycling intraventricular pressure and myocardial contraction, and the heart can undergo profound and deleterious changes in ventricular geometry and function. In the short term (days, weeks), poor healing can lead to infarct expansion and left ventricular dilatation and in some cases to infarct rupture and death. In the long term (months, years), filling pressure, wall stress, and left ventricular volume can increase and propagate adverse remodeling, leading to heart failure and a poor prognosis. 7, 9, 10 Conversely,“sufficient” healing preserves left ventricular geometry and prevents heart failure. In this review, we propose that the quality of infarct healing shortly after injury determines the fate of the patient for years to come.