Tissue Transglutaminase Modulates Vascular Stiffness and Function Through Crosslinking-Dependent and Crosslinking-Independent Functions.
Tissue Transglutaminase Modulates Vascular Stiffness and Function Through Crosslinking-Dependent and Crosslinking-Independent Functions.
复制标题
DOI：
10.1161/jaha.116.004161
复制
发表时间：
2017-02-03
影响因子：
5.4
通讯作者：
Santhanam L
中科院分区：
文献类型：
--
作者：
Steppan J;Bergman Y;Viegas K;Armstrong D;Tan S;Wang H;Melucci S;Hori D;Park SY;Barreto SF;Isak A;Jandu S;Flavahan N;Butlin M;An SS;Avolio A;Berkowitz DE;Halushka MK;Santhanam L
血管壁的结构成分，即细胞外基质和平滑肌细胞（SMCs），有助于血管的整体刚度。在这项研究中，我们研究了组织转谷氨酰胺酶（TG2）在血管功能和硬度中的交联依赖性和非交联依赖性作用。从TG2−/−和野生型（WT）小鼠的主动脉中分离SMCs。采用电细胞-衬底阻抗传感和PicoGreen法检测细胞粘附。用博伊登室法检测细胞运动。通过电细胞-底物阻抗传感和EdU掺入试验检测细胞增殖。采用磁扭转细胞术和纳米微球示踪运动研究细胞微观力学。通过拉伸试验检测主动脉力学。血管反应性用钢丝肌图观察。与WT小鼠相比，TG2 - / -小鼠的SMCs粘附延迟，运动能力降低，脱粘和增殖速度加快。TG2 - / - SMCs比WT小鼠更硬，细胞骨架重塑事件更少。TG2 - / - SMCs中的胶原组装延迟，并通过腺病毒转导TG2恢复。TG2−/−小鼠的主动脉环僵硬程度低于WT小鼠；与不依赖交联功能的豚鼠肝脏TG2孵育后，硬度部分恢复。与WT相比，TG2−/−环对苯肾上腺素介导的血管收缩反应增强。在人冠状动脉、血管介质和斑块中，观察到高丰度的纤维连接蛋白表达，并与TG2共定位。TG2通过独立于交联功能的改变SMC收缩力来调节血管功能/张力，并通过调节SMC增殖和基质重塑来调节血管硬度。
The structural elements of the vascular wall, namely, extracellular matrix and smooth muscle cells (SMCs), contribute to the overall stiffness of the vessel. In this study, we examined the crosslinking‐dependent and crosslinking‐independent roles of tissue transglutaminase (TG2) in vascular function and stiffness. SMCs were isolated from the aortae of TG2−/− and wild‐type (WT) mice. Cell adhesion was examined by using electrical cell–substrate impedance sensing and PicoGreen assay. Cell motility was examined using a Boyden chamber assay. Cell proliferation was examined by electrical cell–substrate impedance sensing and EdU incorporation assays. Cell micromechanics were studied using magnetic torsion cytometry and spontaneous nanobead tracer motions. Aortic mechanics were examined by tensile testing. Vasoreactivity was studied by wire myography. SMCs from TG2−/− mice had delayed adhesion, reduced motility, and accelerated de‐adhesion and proliferation rates compared with those from WT. TG2−/− SMCs were stiffer and displayed fewer cytoskeletal remodeling events than WT. Collagen assembly was delayed in TG2−/− SMCs and recovered with adenoviral transduction of TG2. Aortic rings from TG2−/− mice were less stiff than those from WT; stiffness was partly recovered by incubation with guinea pig liver TG2 independent of crosslinking function. TG2−/− rings showed augmented response to phenylephrine‐mediated vasoconstriction when compared with WT. In human coronary arteries, vascular media and plaque, high abundance of fibronectin expression, and colocalization with TG2 were observed. TG2 modulates vascular function/tone by altering SMC contractility independent of its crosslinking function and contributes to vascular stiffness by regulating SMC proliferation and matrix remodeling.
影响因子：
3.7
作者：
Halushka, Marc K.;Cornish, Toby C.;Lu, Jie;Selvin, Steve;Selvin, Elizabeth
通讯作者：
Selvin, Elizabeth