Role of the microtubule network in the passive anisotropic viscoelasticity of right ventricle with pulmonary hypertension progression
Role of the microtubule network in the passive anisotropic viscoelasticity of right ventricle with pulmonary hypertension progression
复制标题
微管网络在肺动脉高压进展右心室被动各向异性粘弹性中的作用
DOI：
10.1016/j.actbio.2024.01.023
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发表时间：
2024
影响因子：
9.7
通讯作者：
Wang, Zhijie
中科院分区：
文献类型：
--
作者：
LeBar, Kristen;Liu, Wenqiang;Pang, Jassia;Chicco, Adam J.;Wang, Zhijie
心肌细胞具有粘弹性，对右心室（RV）力学有重要影响。微管是一种细胞骨架蛋白，已被证明可以调节心肌细胞的粘弹性。此外，来自衰竭心肌的肥厚心肌细胞微管和细胞硬度增加。微管对RV失效中组织级粘弹性行为的影响尚不清楚。我们的目的是研究微管在肺动脉高压（PH）进展过程中右心室自由壁（RVFW）被动各向异性粘弹性中的作用。健康大鼠和PH大鼠在舒张早期（6%）和舒张末期（15%）以及亚（1Hz）和生理（5Hz）拉伸速率下进行RVFW等双轴应力松弛试验。测定微管在5Hz下解聚前后的RVFW粘弹性。在完整组织中，PH在拉伸速率和应变水平上都增加了RV的粘度和弹性，并且在周向的增加强于纵向的增加。在6%的应变下，去除微管降低了两个方向上的弹性、粘度和粘弹性比，对健康和患病的rv都是如此。然而，在15%的应变下，微管的作用在两组之间是不同的——健康的RVs粘度和弹性都降低了，而在患病的RVs中，只有周向粘度和粘弹性比降低了。这些数据表明，在胶原募集的大应变下，微管在健康RV组织弹性和患病RV组织粘度中发挥更重要的作用。我们的研究结果表明，心肌细胞骨架在压力过载下对RV被动粘弹性至关重要。本研究探讨了微管在健康状态和压力过载状态下对右心室自由壁被动各向异性粘弹性的影响。我们最初发现，在舒张早期，微管在纵向和周向两个方向对健康和患病的右心室粘弹性都有显著贡献。在舒张末期（有胶原纤维参与），微管对健康心室的组织弹性和病变心室的组织粘度贡献更大。我们的研究结果揭示了微管在右心室组织各向异性粘弹性中的关键作用，以及从健康状态到患病状态的改变，表明针对微管的治疗可能对右心室衰竭患者有潜在的作用。
Cardiomyocytes are viscoelastic and contribute significantly to right ventricle (RV) mechanics. Microtubule, a cytoskeletal protein, has been shown to regulate cardiomyocyte viscoelasticity. Additionally, hypertrophied cardiomyocytes from failing myocardium have increased microtubules and cell stiffness. How the microtubules contribute to the tissue-level viscoelastic behavior in RV failure remains unknown. Our aim was to investigate the role of the microtubules in the passive anisotropic viscoelasticity of the RV free wall (RVFW) during pulmonary hypertension (PH) progression. Equibiaxial stress relaxation tests were conducted in the RVFW from healthy and PH rats under early (6%) and end (15%) diastolic strains, and at sub- (1Hz) and physiological (5Hz) stretch-rates. The RVFW viscoelasticity was also measured before and after the depolymerization of microtubules at 5Hz. In intact tissues, PH increased RV viscosity and elasticity at both stretch rates and strain levels, and the increase was stronger in the circumferential than longitudinal direction. At 6% of strain, the removal of microtubules reduced elasticity, viscosity, and the ratio of viscosity to elasticity in both directions and for both healthy and diseased RVs. However, at 15% of strain, the effect of microtubules was different between groups – both viscosity and elasticity were reduced in healthy RVs, but in the diseased RVs only the circumferential viscosity and the ratio of viscosity to elasticity were reduced. These data suggest that, at a large strain with collagen recruitment, microtubules play more significant roles in healthy RV tissue elasticity and diseased RV tissue viscosity. Our findings suggest cardiomyocyte cytoskeletons are critical to RV passive viscoelasticity under pressure overload.Statement of SignificanceThis study investigated the impact of microtubules on the passive anisotropic viscoelasticity of the right ventricular (RV) free wall at healthy and pressure-overloaded states. We originally found that the microtubules contribute significantly to healthy and diseased RV viscoelasticity in both (longitudinal and circumferential) directions at early diastolic strains. At end diastolic strains (with the engagement of collagen fibers), microtubules contribute more to the tissue elasticity of healthy RVs and tissue viscosity of diseased RVs. Our findings reveal the critical role of microtubules in the anisotropic viscoelasticity of the RV tissue, and the altered contribution from healthy to diseased state suggests that therapies targeting microtubules may have potentials for RV failure patients.