Impaired smooth muscle cell contractility as a novel concept of abdominal aortic aneurysm pathophysiology
Impaired smooth muscle cell contractility as a novel concept of abdominal aortic aneurysm pathophysiology
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DOI：
10.1038/s41598-019-43322-3
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发表时间：
2019-05-02
影响因子：
4.6
通讯作者：
Yeung, Kak K.
中科院分区：
文献类型：
--
作者：
Bogunovic, Natalija;Meekel, Jorn P.;Yeung, Kak K.
腹主动脉瘤（AAA）破裂的总死亡率高达90%。尽管进行了广泛的研究，但导致AAA形成和发展的机制仍然知之甚少。平滑肌细胞（SMC）在主动脉中层中占主导地位，并维持壁结构。平滑肌细胞凋亡是腹主动脉瘤病理生理学中的一个众所周知的现象。然而，剩余的SMC功能的研究较少。本研究的目的是评估人AAA和非病理性主动脉SMC的体外收缩性。从AAA患者（n = 21）和对照组（n = 6）中采集围手术期活检组织，并收集临床数据。在离子霉素刺激时使用电细胞基质阻抗传感（ECIS）测量收缩性。此外，与对照组相比，23%（5/21）AAA患者的SMC显示最大收缩受损。此外，与对照组相比，早期腔内修复术后接受开放修复术的患者的SMC和当前吸烟者的SMC显示最大收缩降低（分别为p = 0.050和p = 0.030）。我们的应用ECIS可用于研究其他血管疾病的收缩性。最后，我们的研究提供了第一个证据，即受损的SMC收缩性可能在AAA病理生理学中发挥作用。
Ruptured abdominal aortic aneurysms (AAA) are associated with overall mortality rates up to 90%. Despite extensive research, mechanisms leading to AAA formation and advancement are still poorly understood. Smooth muscle cells (SMC) are predominant in the aortic medial layer and maintain the wall structure. Apoptosis of SMC is a well-known phenomenon in the pathophysiology of AAA. However, remaining SMC function is less extensively studied. The aim of this study is to assess the in vitro contractility of human AAA and non-pathologic aortic SMC. Biopsies were perioperatively harvested from AAA patients (n = 21) and controls (n = 6) and clinical data were collected. Contractility was measured using Electric Cell-substrate Impedance Sensing (ECIS) upon ionomycin stimulation. Additionally, SMC of 23% (5 out of 21) of AAA patients showed impaired maximum contraction compared to controls. Also, SMC from patients who underwent open repair after earlier endovascular repair and SMC from current smokers showed decreased maximum contraction vs. controls (p = 0.050 and p = 0.030, respectively). Our application of ECIS can be used to study contractility in other vascular diseases. Finally, our study provides with first proof that impaired SMC contractility might play a role in AAA pathophysiology.