Cardiomyopathy is associated with structural remodelling of heart valve extracellular matrix

被引：43

作者：

Schenke-Layland, Katja ^{[1
,2
]}

Stock, Ulrich A. ^{[2
,3
]}

Nsair, Ali ^{[1
]}

Xie, Jiansong ^{[4
]}

Angelis, Ekaterini ^{[1
]}

Fonseca, Carissa G. ^{[5
]}

Larbig, Robert ^{[1
]}

Mahajan, Aman ^{[6
]}

Shivkumar, Kalyanam ^{[1
]}

Fishbein, Michael C. ^{[7
]}

MacLellan, William R.

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Cardiovasc Res Labs, Dept Med Cardiol, Los Angeles, CA 90095 USA

[2] Univ Jena, Dept Cardiothorac & Vasc Surg, Jena, Germany

[3] Univ Tubingen, Dept Thorac Cardiac & Vasc Surg, Tubingen, Germany

[4] USC, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA USA

[5] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, David Geffen Sch Med, Dept Anaesthesiol, Los Angeles, CA 90095 USA

[7] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol Lab Med, Los Angeles, CA 90095 USA

来源：

EUROPEAN HEART JOURNAL | 2009年 / 30卷 / 18期

基金：

美国国家卫生研究院;

关键词：

Heart valves; Cardiomyopathy; Extracellular matrix; Collagen; Remodelling; AORTIC-STENOSIS; TISSUE; REPLACEMENT; CALCIFICATION; EXPRESSION; ELASTIN; DISEASE; ADULT; CELLS;

D O I：

10.1093/eurheartj/ehp267

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

To increase the supply, many countries harvest allograft valves from explanted hearts of transplant recipients with ischaemic (ICM) or dilated cardiomyopathy (DCM). This study determines the structural integrity of valves from cardiomyopathic hearts. Extracellular matrix (ECM) was examined in human valves obtained from normal, ICM, and DCM hearts. To confirm if ECM changes were directly related to the cardiomyopathy, we developed a porcine model of chronic ICM. Histology and immunohistostaining, as well as non-invasive multiphoton and second harmonic generation (SHG) imaging revealed marked disruption of ECM structures in human valves from ICM and DCM hearts. The ECM was unaffected in valves from normal and acute ICM pigs, whereas chronic ICM specimens showed ECM alterations similar to those seen in ICM and DCM patients. Proteins and proteinases implicated in ECM remodelling, including Tenascin C, TGF beta 1, Cathepsin B, MMP2, were upregulated in human ICM and DCM, and porcine chronic ICM specimens. Valves from cardiomyopathic hearts showed significant ECM deterioration with a disrupted collagen and elastic fibre network. It will be important to determine the impact of this ECM damage on valve durability and calcification in vivo if allografts are to be used from these donors.

引用

页码：2254 / 2265

页数：12

共 29 条

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