Aortic valve disease and treatment: The need for naturally engineered solutions

被引:143
作者
Butcher, Jonathan T. [1 ]
Mahler, Gretchen J. [1 ]
Hockaday, Laura A. [1 ]
机构
[1] Cornell Univ, Dept Biomed Engn, Ithaca, NY USA
基金
美国国家科学基金会;
关键词
Atherosclerosis; Stenosis; Calcification; Risk factors; Heterogeneous; Biomarkers; Congenital heart defects; Genetic mutations; Animal models; Tissue engineering; Biomechanics; Endothelial; Interstitial; Clinical trials; Drug discovery; LOW-DENSITY-LIPOPROTEIN; VALVULAR ENDOTHELIAL-CELLS; ANGIOTENSIN-CONVERTING ENZYME; BIAXIAL MECHANICAL-PROPERTIES; CONGENITAL HEART-DISEASE; C-REACTIVE PROTEIN; HOLT-ORAM-SYNDROME; ELASTOLYTIC CATHEPSIN-S; MESENCHYMAL STEM-CELLS; MUTATIONS CAUSE NOONAN;
D O I
10.1016/j.addr.2011.01.008
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The aortic valve regulates unidirectional flow of oxygenated blood to the myocardium and arterial system. The natural anatomical geometry and microstructural complexity ensures biomechanically and hemodynamically efficient function. The compliant cusps are populated with unique cell phenotypes that continually remodel tissue for long-term durability within an extremely demanding mechanical environment. Alteration from normal valve homeostasis arises from genetic and microenvironmental (mechanical) sources, which lead to congenital and/or premature structural degeneration. Aortic valve stenosis pathobiology shares some features of atherosclerosis, but its final calcification endpoint is distinct. Despite its broad and significant clinical significance, very little is known about the mechanisms of normal valve mechanobiology and mechanisms of disease. This is reflected in the paucity of predictive diagnostic tools, early stage interventional strategies, and stagnation in regenerative medicine innovation. Tissue engineering has unique potential for aortic valve disease therapy, but overcoming current design pitfalls will require even more multidisciplinary effort. This review summarizes the latest advancements in aortic valve research and highlights important future directions. (C) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码:242 / 268
页数:27
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