PHACTR1 and Atherosclerosis: It's Complicated.
PHACTR1 and Atherosclerosis: It's Complicated.
复制标题
PHACTR1 和动脉粥样硬化：很复杂。
DOI：
10.1161/atvbaha.123.319545
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Rezvan,Amir
中科院分区：
文献类型：
--
作者：
Rezvan,Amir
PHACTR1(磷酸酶和肌动蛋白调节蛋白1)在多个基因组范围的关联研究中与冠状动脉疾病有关。然而，研究PHACTR1在动脉粥样硬化中的潜在作用的实验研究描绘了一幅相当复杂的图景。PHACTR1在动脉粥样硬化中的作用可能是通过多种细胞类型介导的，包括巨噬细胞和内皮细胞。总体而言，目前的数据表明PHACTR1在造血细胞中具有动脉粥样硬化保护作用。造血性PHACTR1缺陷导致动脉粥样硬化加重，M1巨噬细胞极化增加，泡沫细胞形成加快，5缺陷巨噬细胞泡出，斑块坏死增加。内皮细胞(ECs)是另一种细胞类型，PHACTR1可通过它影响动脉粥样硬化，更具体地说，影响动脉粥样硬化的局灶性流行。动脉粥样硬化病变主要形成在血管系统暴露于血流模式紊乱的区域，如分叉和弯曲度。EC促进或保护动脉粥样硬化至少部分是通过它们对血流的反应来实现的。动脉树直段内皮细胞暴露于单向层流切应力下，大多是静止的，具有动脉粥样硬化保护表型。相反，暴露在扰动血流中并经历低切应力和振荡切应力的内皮细胞被激活，表现出更高水平的周转和炎症，并具有动脉粥样硬化表型。9-11 EC PHACTR1的作用已被研究，但有争议的结果表明，潜在的前动脉粥样硬化和动脉粥样硬化保护作用。12、13最近的活体研究表明，EC PHACTR1在血管顺应性中起作用，但不影响内皮功能14和非动脉粥样硬化性动脉病变。15到目前为止，还没有进行体内研究来检验EC PHACTR1对动脉粥样硬化的影响，更重要的是，剪切力对EC PHACTR1的影响还没有研究。
PHACTR1 (phosphatase and actin regulator protein 1) has been linked to coronary artery disease in multiple genome-wide association studies. 1–4 However, experimental studies looking at potential roles for PHACTR1 in atherosclerosis have painted a rather complex picture. The effects of PHACTR1 on atherosclerosis are likely mediated via multiple cell types, including macrophages and endothelial cells. Overall, current data suggest an atheroprotective role for PHACTR1 in hematopoietic cells. Hematopoietic PHACTR1 deficiency led to increased atherosclerosis, increased M1 macrophage polarization, accelerated foam cell formation, 5 defective macrophage efferocytosis, and increased plaque necrosis. 6 Endothelial cells (ECs) are another cell type through which PHACTR1 may affect atherosclerosis, and more specifically, the focal prevalence of atherosclerosis. Atherosclerotic lesions predominately form in areas of the vasculature exposed to disturbed flow patterns such as bifurcations and curvatures. 7, 8 EC promote or protect from atherosclerosis at least in part by their response to blood flow. EC in straight segments of the arterial tree are exposed to unidirectional laminar shear stress, are mostly quiescent, and have an atheroprotective phenotype. In contrast, ECs that are exposed to disturbed flow and experience low and oscillatory shear stress are activated, exhibit higher levels of turnover and inflammation, and have an atheroprone phenotype. 9–11 The role of EC PHACTR1 has been studied with controversial results suggesting both potentially proatherogenic and atheroprotective roles. 12, 13 More recently, in vivo studies have shown a role for EC PHACTR1 in vascular compliance but not endothelial function14 and nonatherosclerotic arteriopathies. 15 So far, no in vivo studies have been performed to examine the effect of EC PHACTR1 on atherosclerosis, and importantly, the effect of shear stress on EC PHACTR1 has not yet been studied.