Reverse remodeling of the myocardial extracellular matrix after prolonged left ventricular assist device support follows a biphasic pattern
Reverse remodeling of the myocardial extracellular matrix after prolonged left ventricular assist device support follows a biphasic pattern
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DOI：
10.1016/j.healun.2006.05.011
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发表时间：
2006-09-01
影响因子：
8.9
通讯作者：
de Weger, Roel A.
中科院分区：
文献类型：
--
作者：
Bruggink, Annette H.;van Oosterhout, Matthijs F. M.;de Weger, Roel A.
背景：胶原蛋白是细胞外基质（ECM）的重要组成部分。胶原蛋白结构和组成的改变可导致终末期心力衰竭。左心室辅助装置（LVAD）经常被用作心脏移植（HTx）的桥梁。在这项研究中，我们分析了胶原蛋白的组成以及这些胶原蛋白的合成或降解后，长期LVAD support.Methods的变化：细胞外基质体积进行定量后，苦天狼星红染色。用免疫组织化学（IHC）分析I型和III型胶原蛋白，并使用定量聚合酶链反应（PCR）分析胶原mRNA表达。通过测量血浆中I型胶原的N-末端前肽（PINP）、III型胶原的N-末端前肽（PIIINP）和I型胶原的羧基末端肽（ICTP）来研究胶原的合成和降解。结果：LVAD植入后200天，ECM体积增加。在200至400天之间，ECM体积减少，但仍高于LVAD前。400天后，ECM体积小于LVAD前体积。IHC未显示LVAD前后胶原成分的显著差异。胶原mRNA表达没有变化，但在LVAD支持后的第一个月内，通过测量血浆PINP和PIIINP水平检测到胶原合成增加。此外，质量的胶原网络improved.Conclusions：逆转重构LVAD支持过程中遵循双相模式。最初，发生I型和III型胶原蛋白周转的增加，这被ECM的体积增加所阻碍。随后，这种周转随着ECM体积的减少而减少，这导致胶原蛋白网络的恢复。
Background: Collagens are important components of the extracellular matrix (ECM). Alterations in collagen structure and composition can lead to end-stage heart failure. Left ventricular assist devices (LVADs) are frequently used as a bridge to heart transplantation (HTx). In this study, we analyzed changes in composition of the collagens as well as the synthesis or degradation of these collagens after prolonged LVAD support.Methods: The ECM volume was quantified after Picro-Sirius red staining. With immunohistochemistry (IHC), Type I and Type III collagen proteins were analyzed and, using quantitative polymerase chain reaction (PCR), collagen mRNA expression was analyzed. Collagen synthesis and degradation was studied by measuring N-terminal pro-peptide for Type I collagen (PINP), N-terminal pro-peptide for Type III cotlagen (PIIINP) and carboxyterminal telopeptide for Type I collagen (ICTP) in plasma. Collagen composition was measured using the hydroxyproline/Sircol assay.Results: The ECM volume increased in the first 200 days after LVAD implantation. At between 200 and 400 days the ECM volume decreased, but remained higher than pre-LVAD. After 400 days the ECM volume was smaller than the pre-LVAD volume. IHC did not show a significant difference pre- and post-LVAD for collagen composition. Collagen mRNA expression did not change but an augmented synthesis of collagen during the first month after LVAD support was detected upon measurement of plasma PINP and PIIINP levels. In addition, the quality of the collagen network improved.Conclusions: Reverse remodeling during LVAD support follows a biphasic pattern. Initially, an increase in Type I and Type III collagen turnover occurs, which is paralleled by a volume increase of the ECM. Subsequently, this turnover decreases as ECM volume decreases, which results in a restoration of the collagen network.