Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Circ Res. 2010 Nov 26;107(11):1355-63. doi: 10.1161/CIRCRESAHA.110.229955. Epub 2010 Oct 7.
Hemodynamic forces caused by the altered blood flow in response to an occlusion lead to the induction of collateral remodeling and arteriogenesis. Previous work showed that platelet endothelial cell adhesion molecule (PECAM)-1 is a component of a mechanosensory complex that mediates endothelial cell responses to shear stress.
We hypothesized that PECAM-1 plays an important role in arteriogenesis and collateral remodeling.
PECAM-1 knockout (KO) and wild-type littermates underwent femoral artery ligation. Surprisingly, tissue perfusion and collateral-dependent blood flow were significantly increased in the KO mice immediately after surgery. Histology confirmed larger caliber of preexisting collaterals in the KO mice. Additionally, KO mice showed blunted recovery of perfusion from hindlimb ischemia and reduced collateral remodeling, because of deficits in shear stress-induced signaling, including activation of the nuclear factor κB pathway and inflammatory cell accumulation. Partial recovery was associated with normal responses to circumferential wall tension in the absence of PECAM-1, as evidenced by the upregulation of ephrin B2 and monocyte chemoattractant protein-1, which are 2 stretch-induced regulators of arteriogenesis, both in vitro and in vivo.
Our findings suggest a novel role for PECAM-1 in arteriogenesis and collateral remodeling. Furthermore, we identify PECAM-1 as the first molecule that determines preexisting collateral diameter.
血流改变引起的血液动力学改变导致侧支重塑和动脉生成。以前的工作表明，血小板内皮细胞黏附分子（PECAM-1）是机械敏感复合物的一个组成部分，介导内皮细胞对切应力的反应。
我们假设 PECAM-1 在动脉生成和侧支重塑中起重要作用。
PECAM-1 敲除（KO）和野生型同窝仔鼠进行股动脉结扎。令人惊讶的是，手术后 KO 小鼠的组织灌注和依赖侧支的血流量立即显著增加。组织学证实 KO 小鼠的预存侧支管径更大。此外，由于剪切应力诱导的信号转导缺陷，包括核因子 κB 通路的激活和炎症细胞的积累，KO 小鼠的灌注从后肢缺血中恢复减弱，侧支重塑减少。部分恢复与 PECAM-1 缺失时对周向壁张力的正常反应有关，这表现在 Ephrin B2 和单核细胞趋化蛋白-1 的上调，Ephrin B2 和单核细胞趋化蛋白-1 是体外和体内 2 种动脉生成的拉伸诱导调节因子。
我们的研究结果表明 PECAM-1 在动脉生成和侧支重塑中具有新的作用。此外，我们确定 PECAM-1 是决定预存侧支直径的第一个分子。
