Grobbel M R, Lee L C, Watts S W, Fink G D, Roccabianca S
Michigan State University, Mechanical Engineering Department.
Michigan State University, Pharmacology & Toxicology Department.
Exp Mech. 2021 Jan;61(1):191-201. doi: 10.1007/s11340-020-00664-8. Epub 2020 Sep 14.
Hypertension drives myocardial remodeling, leading to changes in structure, composition and mechanical behavior, including residual stress, which are linked to heart disease progression in a gender-specific manner. Emerging therapies are also targeting constituent-specific pathological features. All previous studies, however, have characterized remodeling in the intact tissue, rather than isolated tissue constituents, and did not include sex as a biological variable.
In this study we first identified the contribution of collagen fiber network and myocytes to the myocardial residual stress/strain in Dahl-Salt sensitive rats fed with high fat diet. Then, we quantified the effect of hypertension on the remodeling of the left ventricle (LV), as well as the existence of sex-specific remodeling features.
We performed mechanical tests (opening angle, ring-test) and histological analysis on isolated constituents and intact tissue of the LV. Based on the measurements from the tests, we performed a stress analysis to evaluate the residual stress distribution. Statistical analysis was performed to identify the effects of constituent isolation, elevated blood pressure, and sex of the animal on the output of both experimental measures and modeling results.
Hypertension leads to reduced residual stress/strain intact tissue, isolated collagen fibers, and isolated myocytes in male and female rats. Collagen remains the largest contributor to myocardial residual stress in both normotensive and hypertensive animals. We identified sex-differences in both hypertensive and normotensive animals.
We observed both constituent- and sex-specific remodeling features in the LV of an animal model of hypertension.
高血压会引发心肌重塑，导致结构、组成和力学行为发生变化，包括残余应力，这些变化以性别特异性方式与心脏病进展相关。新兴疗法也针对特定成分的病理特征。然而，此前所有研究均是对完整组织而非分离的组织成分进行重塑特征描述，且未将性别作为生物学变量纳入研究。
在本研究中，我们首先确定了胶原纤维网络和心肌细胞对高脂饮食喂养的 Dahl-Salt 敏感大鼠心肌残余应力/应变的贡献。然后，我们量化了高血压对左心室（LV）重塑的影响，以及性别特异性重塑特征的存在情况。
我们对 LV 的分离成分和完整组织进行了力学测试（开口角度、环测试）和组织学分析。基于测试测量结果，我们进行了应力分析以评估残余应力分布。进行统计分析以确定成分分离、血压升高和动物性别对实验测量结果和建模结果的影响。
高血压导致雄性和雌性大鼠的完整组织、分离的胶原纤维和分离的心肌细胞中的残余应力/应变降低。在正常血压和高血压动物中，胶原仍然是心肌残余应力的最大贡献者。我们在高血压和正常血压动物中均发现了性别差异。
我们在高血压动物模型的 LV 中观察到了成分特异性和性别特异性的重塑特征。
