Durbin Adam D, Gotlieb Avrum I
Toronto General Research Institute, Toronto, Ontario, Canada.
Cardiovasc Pathol. 2002 Mar-Apr;11(2):69-77. doi: 10.1016/s1054-8807(01)00109-0.
Composed of endocardial endothelial, valvular interstitial, cardiac muscle, and smooth muscle cells (SMC), heart valves are prone to various pathologic conditions the morphology of which has been well described. The morphology of diseased valves suggest that the "response to injury" process occurs in these valves, and is associated with an accumulation of interstitial cells and matrix, valvular inflammation and calcification, conditions that lead to dysfunction. The purpose of this study is to describe the current knowledge of the regulation of the valvular "response to injury" process, since we feel that this paradigm is essential to understanding valve disease.
The pertinent literature relating to the cell and molecular biology of valvular repair, and specifically interstitial cell function in valve repair, is reviewed.
The cell and molecular biology of valve interstitial cells are poorly understood. Molecules regulating some of the aspects of the "response to injury" process have been studied, however, the signal transduction pathways, gene activation, and interactions of bioactive molecules with each other, with cells, and with the matrix have not been characterized. Initial studies identify the cell and molecular biology of interstitial cells to be an important area of research. Agents that have been studied include nitric oxide (NO) and FGF-2 and several matrix-related proteins including osteopontin. The present review suggests several directions for future study and a working model of valvular repair is presented.
The regulation of the "response to injury" process in the human heart valve is still largely unknown. The cell and molecular events and processes that occur in heart valve function and repair remain poorly understood. These events and processes are vital to our understanding of the pathobiology of heart valve disease, and to the successful design of tissue engineered replacement valves.
心脏瓣膜由心内膜内皮细胞、瓣膜间质细胞、心肌细胞和平滑肌细胞组成，易发生多种病理状况，其形态已得到充分描述。病变瓣膜的形态表明，“损伤反应”过程在这些瓣膜中发生，并与间质细胞和基质的积聚、瓣膜炎症和钙化相关，这些情况会导致功能障碍。本研究的目的是描述目前关于瓣膜“损伤反应”过程调节的知识，因为我们认为这一模式对于理解瓣膜疾病至关重要。
回顾了与瓣膜修复的细胞和分子生物学相关的文献，特别是瓣膜修复中间质细胞的功能。
对瓣膜间质细胞的细胞和分子生物学了解甚少。虽然已经研究了调节“损伤反应”过程某些方面的分子，但信号转导途径、基因激活以及生物活性分子之间、与细胞之间以及与基质之间的相互作用尚未得到明确。初步研究确定间质细胞的细胞和分子生物学是一个重要的研究领域。已研究的因子包括一氧化氮（NO）、成纤维细胞生长因子-2（FGF-2）以及几种与基质相关的蛋白质，包括骨桥蛋白。本综述提出了未来研究的几个方向，并给出了瓣膜修复的工作模型。
人类心脏瓣膜“损伤反应”过程的调节在很大程度上仍然未知。心脏瓣膜功能和修复过程中发生的细胞和分子事件及过程仍了解不足。这些事件和过程对于我们理解心脏瓣膜疾病的病理生物学以及成功设计组织工程置换瓣膜至关重要。
