Bruggink Annette H, van Oosterhout Matthijs F M, de Jonge Nicolaas, Ivangh Bas, van Kuik Joyce, Voorbij Ron H A M, Cleutjens Jack P M, Gmelig-Meyling Frits H J, de Weger Roel A
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
J Heart Lung Transplant. 2006 Sep;25(9):1091-8. doi: 10.1016/j.healun.2006.05.011. Epub 2006 Aug 2.
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.
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 collagen (PIIINP) and carboxyterminal telopeptide for Type I collagen (ICTP) in plasma. Collagen composition was measured using the hydroxyproline/Sircol assay.
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.
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.
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）常被用作心脏移植（HTx）的桥梁。在本研究中，我们分析了长期LVAD支持后胶原蛋白组成的变化以及这些胶原蛋白的合成或降解情况。
用天狼星红苦味酸染色后对ECM体积进行定量。采用免疫组织化学（IHC）分析I型和III型胶原蛋白蛋白，并使用定量聚合酶链反应（PCR）分析胶原蛋白mRNA表达。通过测量血浆中I型胶原蛋白的N端前肽（PINP）、III型胶原蛋白的N端前肽（PIIINP）和I型胶原蛋白的羧基末端肽（ICTP）来研究胶原蛋白的合成和降解。使用羟脯氨酸/Sircol分析法测量胶原蛋白组成。
LVAD植入后的前200天ECM体积增加。在200至400天之间，ECM体积减小，但仍高于LVAD植入前。400天后，ECM体积小于LVAD植入前的体积。IHC显示LVAD前后胶原蛋白组成无显著差异。胶原蛋白mRNA表达没有变化，但通过测量血浆PINP和PIIINP水平发现在LVAD支持后的第一个月胶原蛋白合成增加。此外，胶原蛋白网络的质量得到改善。
LVAD支持期间的逆向重塑呈双相模式。最初，I型和III型胶原蛋白周转率增加，同时ECM体积增加。随后，随着ECM体积减小，这种周转率降低，从而导致胶原蛋白网络的恢复。
