Contribution of titin and extracellular matrix to passive pressure and measurement of sarcomere length in the mouse left ventricle.
Contribution of titin and extracellular matrix to passive pressure and measurement of sarcomere length in the mouse left ventricle.
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DOI：
10.1016/j.yjmcc.2011.01.005
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发表时间：
2011-04
影响因子：
5
通讯作者：
Granzier HL
中科院分区：
文献类型：
--
作者：
Chung CS;Granzier HL
肌联蛋白和细胞外基质 (ECM) 对左心室 (LV) 被动压力的影响程度仍有待确定。因此，我们的目的是阐明正常小鼠左心室被动压力的主要分子决定因素的作用。此外，我们确定了 LV 的工作肌节长度 (SL) 范围，以将我们的发现与早期的带皮肌纤维工作联系起来。我们利用 Frank-Starling 型协议来获得 Langendorff 灌注的隔离左心室中的舒张压-容积关系 (PVR)。为了量化肌联蛋白和 ECM 的分子贡献，我们创新了纤维力学方法，对完整的 LV 进行化学透化并测量完全被动的 PVR。为了差异化剖析 ECM 和肌联蛋白的贡献，我们在透化 LV 中利用肌丝提取技术，测量方案中每个阶段的被动 PVR。肌丝提取表明肌联蛋白贡献了约 80% 的心脏被动压力。 Langendorff 灌注还用于以化学方式固定特定体积的被动心脏和 BaCl2 激活心脏，以确定中壁 LV 纤维的最大工作 SL 范围约为 1.8-2.2 μm。然后使用被动 SL-体积关系模型来估计压力-SL 关系，表明 ECM 贡献不会超过 titin 的贡献，直到 SL>~2.2μm 的大体积。总之，在生理体积内，肌动蛋白是左心室被动压力的主要贡献者，而基于 ECM 的压力在较大体积内占主导地位。
It remains to be established to what degree titin and the extracellular matrix (ECM) contribute to passive pressure in the left ventricle (LV). Thus, we aimed to elucidate the contribution of major molecular determinants of passive pressure in the normal mouse LV. Furthermore, we determined the working sarcomere length (SL) range of the LV to bridge our findings to earlier work in skinned muscle fibers. We utilized Frank-Starling type protocols to obtain diastolic pressure-volume relationships (PVR) in Langendorff perfused isolated LVs. To quantify the molecular contribution of titin and ECM, we innovated on methods of fiber mechanics to chemically permeabilize intact LVs and measure a fully passive PVR. To differentially dissect the contributions of the ECM and titin, we utilized myofilament extraction techniques in permeabilized LVs, measuring passive PVRs at each stage in the protocol. Myofilament extraction suggests that titin contributes ~80% of passive pressures in the heart. Langendorff perfusion was also used to chemically fix passive and BaCl2 activated hearts at specific volumes to determine that the maximal working SL range of the midwall LV fibers is approximately 1.8-2.2 μm. A model of the passive SL-Volume relationship was then used to estimate the pressure-SL relationships, indicating that the ECM contribution does not exceed titin's contribution until large volumes with SLs>~2.2μm. In conclusion, within physiological volumes titin is the dominant contributor to LV passive pressure, and ECM-based pressures dominates at larger volumes.
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影响因子：
20.1
作者：
Hidalgo C;Hudson B;Bogomolovas J;Zhu Y;Anderson B;Greaser M;Labeit S;Granzier H
通讯作者：
Granzier H
影响因子：
33.6
作者：
Kontrogianni-Konstantopoulos A;Ackermann MA;Bowman AL;Yap SV;Bloch RJ
通讯作者：
Bloch RJ
影响因子：
56.9
作者：
LABEIT, S;KOLMERER, B
通讯作者：
KOLMERER, B
影响因子：
3.4
作者：
Kocica, Mladen J.;Corno, Antonio F.;Torrent-Guasp, Francisco
通讯作者：
Torrent-Guasp, Francisco
影响因子：
3.4
作者：
LINKE, WA;POPOV, VI;POLLACK, GH
通讯作者：
POLLACK, GH