Cell communications in the heart.
Cell communications in the heart.
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DOI：
10.1161/circulationaha.108.847731
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发表时间：
2010-08-31
期刊：
影响因子：
37.8
通讯作者：
Simons M
中科院分区：
文献类型：
--
作者：
Tirziu D;Giordano FJ;Simons M
有效的心肌功能主要取决于氧化能量的产生。对于人类来说，心率为每分钟 60 至 70 次时，每克心肌的标准化耗氧量比静息时骨骼肌的耗氧量高 20 倍。为了适应这种高耗氧量，心脏保持 70% 至 80% 的高水平吸氧，而骨骼肌为 30% 至 40%。 2 骨骼肌中每 1 mm2 的毛细血管密度为 3000 至 4000 个，而骨骼肌中的毛细血管密度为 500 至 2000 个，并且对冠状动脉血流进行严格调节，这有助于实现这一点。 3 在运动引起的肥大的情况下，心脏保留氧气供应/需求，与心肌细胞大小和冠状微脉管系统范围的成比例增加相匹配。 3, 4 不同形式的血流动力学应激（高血压、主动脉瓣狭窄、主动脉缩窄、二尖瓣反流和心肌梗塞等）会增加心室内压力或容量并导致肥厚反应。 5 由于持续的心肌细胞死亡和纤维化，室壁应力的长期增加可能导致进行性心室扩张和心肌失代偿，并最终导致心力衰竭和死亡。 6, 7 这种病理进展表明氧气供应和需求之间不匹配，因为心肌细胞肥大的程度与动脉血液供应的相应增加不匹配。 3 人类心脏估计含有 2 至 30 亿个心肌细胞，但它们只占心脏细胞总数的不到三分之一。平衡包括多种其他细胞类型，包括冠状脉管系统和心内膜的平滑肌和内皮细胞、成纤维细胞和其他结缔组织细胞、肥大细胞和免疫系统相关细胞。最近，在心脏中也发现了多能心脏“干细胞”。 8 这些不同的细胞池在心脏内并不是彼此隔离的，而是通过各种可溶性旁分泌、自分泌和内分泌因子进行物理相互作用（总结于图 1）。因此，为了充分了解心脏的生物学和病理学，必须考虑这种细胞串扰的影响。在这篇综述中，我们讨论了对心肌肥厚反应的分子调节的新见解，重点关注心脏中细胞间串扰对此过程的贡献。
Effective myocardial function depends primarily on oxidative energy production. In humans, at a heart rate of 60 to 70 beats per minute, the oxygen consumption normalized per gram of myocardium is 20-fold higher than that of skeletal muscle at rest. As an adaptation to this high oxygen demand, the heart maintains a high level of oxygen extraction of 70% to 80% compared with 30% to 40% in skeletal muscle. 2 This is facilitated by the capillary density of 3000 to 4000 compared with 500 to 2000 per 1 mm2 in skeletal muscle and a tight regulation of the coronary blood flow. 3 In the case of exercise-induced hypertrophy, the heart preserves the oxygen supply/demand, matching the proportional increases in cardiac myocyte size and the extent of coronary microvasculature. 3, 4 Different forms of hemodynamic stress (hypertension, aortic stenosis, coarctation of the aorta, mitral regurgitation, and myocardial infarction, among others) increase intraventricular pressure or volume and lead to a hypertrophic response. 5 A prolonged increase in wall stress may result in progressive ventricular dilation and myocardial decompensation owing to ongoing myocyte death and fibrosis and, ultimately, heart failure and death. 6, 7 This pathological progression demonstrates a mismatch between oxygen supply and demand, as the extent of cardiomyocyte hypertrophy is not matched by a corresponding increase in the arterial blood supply. 3 The human heart contains an estimated 2 to 3 billion cardiac muscle cells, but they account for fewer than a third of the total number of cells in the heart. The balance includes a broad array of additional cell types, including smooth muscle and endothelial cells of the coronary vasculature and the endocardium, fibroblasts and other connective tissue cells, mast cells, and immune system–related cells. Recently, pluripotent cardiac “stem cells” have also been identified in the heart. 8 These distinct cell pools are not isolated from one another within the heart but instead interact physically and via a variety of soluble paracrine, autocrine, and endocrine factors (summarized in Figure 1). Thus, to fully understand the biology and pathobiology of the heart, the influences of this cellular crosstalk must be considered. In this review, we discuss new insights into molecular regulation of a myocardial hypertrophic response, focusing on the contribution of cell-cell crosstalk in the heart to this process.