MacGrogan Donal, Luxán Guillermo, Driessen-Mol Anita, Bouten Carlijn, Baaijens Frank, de la Pompa José Luis
Program of Cardiovascular Developmental Biology, Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
Biomedical Engineering/Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands.
Cold Spring Harb Perspect Med. 2014 Nov 3;4(11):a013912. doi: 10.1101/cshperspect.a013912.
Cardiac valve disease is a significant cause of ill health and death worldwide, and valve replacement remains one of the most common cardiac interventions in high-income economies. Despite major advances in surgical treatment, long-term therapy remains inadequate because none of the current valve substitutes have the potential for remodeling, regeneration, and growth of native structures. Valve development is coordinated by a complex interplay of signaling pathways and environmental cues that cause disease when perturbed. Cardiac valves develop from endocardial cushions that become populated by valve precursor mesenchyme formed by an epithelial-mesenchymal transition (EMT). The mesenchymal precursors, subsequently, undergo directed growth, characterized by cellular compartmentalization and layering of a structured extracellular matrix (ECM). Knowledge gained from research into the development of cardiac valves is driving exploration into valve biomechanics and tissue engineering directed at creating novel valve substitutes endowed with native form and function.
心脏瓣膜疾病是全球范围内导致健康问题和死亡的重要原因，在高收入经济体中，瓣膜置换仍然是最常见的心脏干预措施之一。尽管外科治疗取得了重大进展，但长期治疗仍然不足，因为目前的瓣膜替代品都没有重塑、再生和生长天然结构的潜力。瓣膜发育由信号通路和环境信号的复杂相互作用协调，这些信号通路和环境信号受到干扰时会引发疾病。心脏瓣膜由心内膜垫发育而来，心内膜垫被上皮-间充质转化（EMT）形成的瓣膜前体间充质填充。随后，间充质前体经历定向生长，其特征是细胞分隔和结构化细胞外基质（ECM）的分层。从心脏瓣膜发育研究中获得的知识正在推动对瓣膜生物力学和组织工程的探索，旨在创造具有天然形态和功能的新型瓣膜替代品。
