Biomechanical assessment of remote and postinfarction scar remodeling following myocardial infarction
Biomechanical assessment of remote and postinfarction scar remodeling following myocardial infarction
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DOI：
10.1038/s41598-019-53351-7
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发表时间：
2019-11-14
影响因子：
4.6
通讯作者：
Liehn, Elisa A.
中科院分区：
文献类型：
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作者：
Rusu, Mihaela;Hilse, Katrin;Liehn, Elisa A.
心肌梗死(MI)后胶原重构的重要性已被广泛研究，但对心肌梗死后胶原纤维对左心室的生物力学影响知之甚少。我们的目标是确定I型、III型和V型胶原的生物力学在导致心力衰竭的小鼠心脏的生理病理变化中的重要作用。心肌梗死后即刻心脏功能降低(EF=40.94+/-2.12%)，而肌节大小无明显变化。值得注意的是，免疫组织化学染色显示，V型胶原部分在远端和瘢痕中显著生长，以支持I型和III型胶原纤维的组装，同时阻碍其酶降解。此后，代偿性心功能(EF=63.04+/-3.16%)与I型和III型胶原在僵硬的远处(12.79+/-1.09 Mpa)和瘢痕(22.40+/-1.08 Mpa)的稳定发展有关。在远端，柔软的新生III型胶原解卷，防止细长肌节进一步扩张(2.7+/-0.3 mm)。一旦超过了代偿机制，刚性I型胶原(>；50%)的周转增加会导致心脏的假稳定生物力学状态(相当于9兆帕)，EF降低(50.55+/-3.25%)。这些末端特征代表了心肌梗死后心力衰竭患者的常见场景。我们的临床前数据促进了对延迟性心肌梗死患者心力衰竭原因的理解。
The importance of collagen remodeling following myocardial infarction (MI) is extensively investigated, but little is known on the biomechanical impact of fibrillar collagen on left ventricle post-MI. We aim to identify the significant effects of the biomechanics of types I, III, and V collagen on physiopathological changes of murine hearts leading to heart failure. Immediately post-MI, heart reduces its function (EF=40.94 +/- 2.12%) while sarcomeres' dimensions are unchanged. Strikingly, as determined by immunohistochemistry staining, type V collagen fraction significantly grows in remote and scar for sustaining de novo-types I and III collagen fibers' assembly while hindering their enzymatic degradation. Thereafter, the compensatory heart function (EF=63.04 +/- 3.16%) associates with steady development of types I and III collagen in a stiff remote (12.79 +/- 1.09 MPa) and scar (22.40 +/- 1.08 MPa). In remote, the soft de novo-type III collagen uncoils preventing further expansion of elongated sarcomeres (2.7 +/- 0.3 mm). Once the compensatory mechanisms are surpassed, the increased turnover of stiff type I collagen (>50%) lead to a pseudo-stable biomechanical regime of the heart (congruent to 9 MPa) with reduced EF (50.55 +/- 3.25%). These end-characteristics represent the common scenario evidenced in patients suffering from heart failure after MI. Our pre-clinical data advances the understanding of the cause of heart failure induced in patients with extended MI.