Biology and Biomechanics of the Heart Valve Extracellular Matrix.
Biology and Biomechanics of the Heart Valve Extracellular Matrix.
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DOI：
10.3390/jcdd7040057
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发表时间：
2020-12-16
影响因子：
2.4
通讯作者：
Lincoln J
中科院分区：
文献类型：
--
作者：
Kodigepalli KM;Thatcher K;West T;Howsmon DP;Schoen FJ;Sacks MS;Breuer CK;Lincoln J
心脏瓣膜是动态结构，平均每人每天打开和关闭超过100，000次，一生中打开和关闭超过3 × 109次，以维持单向血液流动。在心动周期期间瓣膜结构的有效、协调的运动由细胞外基质（ECM）组分的复杂和精密的网络介导，所述ECM组分提供必要的生物力学性质以满足这些机械需求。心脏瓣膜ECM以适应瓣膜小叶被动功能运动的层组织，在胚胎发育期间合成，并在整个生命过程中由驻留细胞重塑和维持。ECM组织的失效会损害生物力学功能，并可能导致阻塞或泄漏，如果不及时治疗，可能会导致心力衰竭。目前，对心脏瓣膜功能障碍的有效治疗是有限的，并且经常以手术修复或置换结束，这对许多高风险患者（包括老年人和儿童人群）带来了无法克服的并发症。因此，迫切需要充分了解生物力学瓣膜衰竭的病理生物学，以便开发更好的替代疗法。迄今为止，大多数研究都集中在描绘细胞水平上的瓣膜疾病机制，即间质和内皮谱系。然而，较少关注ECM，以前在其他系统中显示，是一个有前途的机制启发的治疗靶点。在这里，我们强调和审查的心脏瓣膜ECM的关键组成部分的生物学和生物力学的贡献。此外，我们讨论了人类疾病，包括结缔组织疾病如何导致这些基质蛋白的丰度，组织和质量的畸变，导致瓣膜基础结构的不稳定和严重的功能障碍。
Heart valves are dynamic structures that, in the average human, open and close over 100,000 times per day, and 3 × 109 times per lifetime to maintain unidirectional blood flow. Efficient, coordinated movement of the valve structures during the cardiac cycle is mediated by the intricate and sophisticated network of extracellular matrix (ECM) components that provide the necessary biomechanical properties to meet these mechanical demands. Organized in layers that accommodate passive functional movements of the valve leaflets, heart valve ECM is synthesized during embryonic development, and remodeled and maintained by resident cells throughout life. The failure of ECM organization compromises biomechanical function, and may lead to obstruction or leaking, which if left untreated can lead to heart failure. At present, effective treatment for heart valve dysfunction is limited and frequently ends with surgical repair or replacement, which comes with insuperable complications for many high-risk patients including aged and pediatric populations. Therefore, there is a critical need to fully appreciate the pathobiology of biomechanical valve failure in order to develop better, alternative therapies. To date, the majority of studies have focused on delineating valve disease mechanisms at the cellular level, namely the interstitial and endothelial lineages. However, less focus has been on the ECM, shown previously in other systems, to be a promising mechanism-inspired therapeutic target. Here, we highlight and review the biology and biomechanical contributions of key components of the heart valve ECM. Furthermore, we discuss how human diseases, including connective tissue disorders lead to aberrations in the abundance, organization and quality of these matrix proteins, resulting in instability of the valve infrastructure and gross functional impairment.
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影响因子：
5.8
作者：
Ayoub S;Ferrari G;Gorman RC;Gorman JH;Schoen FJ;Sacks MS
通讯作者：
Sacks MS
影响因子：
3.8
作者：
Amini, Rouzbeh;Eckert, Chad E.;Koomalsingh, Kevin;McGarvey, Jeremy;Minakawa, Masahito;Gorman, Joseph H.;Gorman, Robert C.;Sacks, Michael S.
通讯作者：
Sacks, Michael S.
影响因子：
5
作者：
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DOI：
10.1152/ajpheart.00277.2018
发表时间：
2018-12-01
影响因子：
4.8
作者：
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通讯作者：
Merryman, W. David
DOI：
10.1002/ajmg.c.31553
发表时间：
2017-03-01
影响因子：
3.1
作者：
Byers, Peter H.;Belmont, John;Wheeldon, Nigel
通讯作者：
Wheeldon, Nigel