Adventitial remodeling protects against aortic rupture following late smooth muscle-specific disruption of TGFβ signaling.
Adventitial remodeling protects against aortic rupture following late smooth muscle-specific disruption of TGFβ signaling.
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DOI：
10.1016/j.jmbbm.2020.104264
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发表时间：
2021-04
影响因子：
3.9
通讯作者：
Humphrey JD
中科院分区：
文献类型：
--
作者：
Kawamura Y;Murtada SI;Gao F;Liu X;Tellides G;Humphrey JD
通过转化生长因子- β (tgf - β)改变的信号会增加患者主动脉夹层的风险，这一点已在小鼠模型中得到证实。众所周知，tgf - β信号的改变会影响基质的周转，但尚未对结构-功能关系的相关变化进行仔细的研究。在本文中，我们提出了在具有夹层易感性的小鼠模型中，出生后晚期平滑肌细胞（SMC）特异性破坏I型和II型TGFβ受体后主动脉壁破裂电位的新发现。通过结合计算机控制的双轴测试和定量组织学和免疫组织化学，我们发现SMCs中TGFβ信号的丢失会损害其医学特性，但会引起外膜的代偿性变化，从而保持壁强度高于抵抗体内壁应力值所需的强度。这些发现强调了导致主动脉夹层和破裂的不同结构缺陷——内侧完整性受损和外膜强度不足。在特定时间的个体受试者中，这两种缺陷的相对差异可能反映了相当大的表型多样性，这在胸主动脉夹层和破裂的临床表现中是常见的。因此，有必要从大量生物分析和壁特性的检查转向细胞和层特异性研究，以描述壁生物学和组成的病理和代偿性变化，从而确定主动脉壁的结构完整性，这可以决定生死之间的差异。
Altered signaling through transforming growth factor-beta (TGFβ) increases the risk of aortic dissection in patients, which has been confirmed in mouse models. It is well known that altered TGFβ signaling affects matrix turnover, but there has not been a careful examination of associated changes in structure-function relations. In this paper, we present new findings on the rupture potential of the aortic wall following late postnatal smooth muscle cell (SMC)-specific disruption of type I and II TGFβ receptors in a mouse model with demonstrated dissection susceptibility. Using a combination of custom computer-controlled biaxial tests and quantitative histology and immunohistochemistry, we found that loss of TGFβ signaling in SMCs compromises medial properties but induces compensatory changes in the adventitia that preserve wall strength above that which is needed to resist in vivo values of wall stress. These findings emphasize the different structural defects that lead to aortic dissection and rupture – compromised medial integrity and insufficient adventitial strength, respectively. Relative differences in these two defects, in an individual subject at a particular time, likely reflects the considerable phenotypic diversity that is common in clinical presentations of thoracic aortic dissection and rupture. There is, therefore, a need to move beyond examinations of bulk biological assays and wall properties to cell- and layer-specific studies that delineate pathologic and compensatory changes in wall biology and composition, and thus the structural integrity of the aortic wall that can dictate differences between life and death.
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影响因子：
10.8
作者：
Inamoto, Sakiko;Kwartler, Callie S.;Milewicz, Dianna M.
通讯作者：
Milewicz, Dianna M.
DOI：
10.1080/10255842.2010.520704
发表时间：
2012-01-01
影响因子：
1.6
作者：
Garcia-Herrera, Claudio M.;Celentano, Diego J.;Goicolea, Jose M.
通讯作者：
Goicolea, Jose M.
影响因子：
3.5
作者：
Korneva, A.;Zilberberg, L.;Bellini, C.
通讯作者：
Bellini, C.
影响因子：
3.9
作者：
Bellini, C.;Bersi, M. R.;Humphrey, J. D.
通讯作者：
Humphrey, J. D.
影响因子：
20.1
作者：
Humphrey JD;Schwartz MA;Tellides G;Milewicz DM
通讯作者：
Milewicz DM