Potential drug targets for calcific aortic valve disease

被引:118
作者
Hutcheson, Joshua D. [1 ]
Aikawa, Elena [2 ]
Merryman, W. David [3 ,4 ]
机构
[1] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Interdisciplinary Cardiovasc Sci, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Excellence Vasc Biol, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Life Sci Boston, Boston, MA 02115 USA
[4] Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37212 USA
关键词
GROWTH-FACTOR-BETA; BONE MORPHOGENETIC PROTEIN-2; VALVULAR ENDOTHELIAL-CELLS; ELASTOLYTIC CATHEPSIN-S; INTERSTITIAL-CELLS; VASCULAR CALCIFICATION; PLAQUE STABILIZATION; SIGNALING PATHWAYS; 5-HT2B RECEPTORS; MATRIX VESICLES;
D O I
10.1038/nrcardio.2014.1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Calcific aortic valve disease (CAVD) is a major contributor to cardiovascular morbidity and mortality and, given its association with age, the prevalence of CAVD is expected to continue to rise as global life expectancy increases. No drug strategies currently exist to prevent or treat CAVD. Given that valve replacement is the only available clinical option, patients often cope with a deteriorating quality of life until diminished valve function demands intervention. The recognition that CAVD results from active cellular mechanisms suggests that the underlying pathways might be targeted to treat the condition. However, no such therapeutic strategy has been successfully developed to date. One hope was that drugs already used to treat vascular complications might also improve CAVD outcomes, but the mechanisms of CAVD progression and the desired therapeutic outcomes are often different from those of vascular diseases. Therefore, we discuss the benchmarks that must be met by a CAVD treatment approach, and highlight advances in the understanding of CAVD mechanisms to identify potential novel therapeutic targets.
引用
收藏
页码:218 / 231
页数:14
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