Chronic sympathetic driven hypertension promotes atherosclerosis by enhancing hematopoiesis.
Chronic sympathetic driven hypertension promotes atherosclerosis by enhancing hematopoiesis.
复制标题
慢性交感神经驱动的高血压通过增强造血作用促进动脉粥样硬化。
DOI：
10.3324/haematol.2018.192898
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发表时间：
2019-03
期刊：
影响因子：
10.1
通讯作者：
Murphy AJ
中科院分区：
文献类型：
--
作者：
Al-Sharea A;Lee MKS;Whillas A;Michell DL;Shihata WA;Nicholls AJ;Cooney OD;Kraakman MJ;Veiga CB;Jefferis AM;Jackson K;Nagareddy PR;Lambert G;Wong CHY;Andrews KL;Head GA;Chin-Dusting J;Murphy AJ
高血压是动脉粥样硬化性心血管疾病的主要独立危险因素。然而，这种病理学可以通过多种途径出现，这可能通过不同的机制影响血管疾病。过度活跃的交感神经系统是导致血压升高的主要途径。我们的目的是确定交感神经系统如何直接促进动脉粥样硬化在高血压的设置。我们使用了一个交感神经系统驱动的高血压的小鼠模型动脉粥样硬化倾向的载脂蛋白E缺乏的背景。当小鼠被放置在西方类型的饮食16周，我们显示了不稳定的动脉粥样硬化病变的演变。幸运的是，病变成分的变化是独立的内皮功能障碍，允许发现替代机制。利用流式细胞术和骨髓成像，我们发现交感神经激活引起骨髓中造血干细胞和祖细胞龛的恶化，促进这些细胞释放到循环和脾中的髓外造血。具体而言，交感神经激活减少了关键的造血干细胞和祖细胞龛细胞，窦内皮细胞和成骨细胞的丰度。此外，交感神经骨髓活性促使中性粒细胞分泌蛋白酶以切割造血干细胞和祖细胞表面受体CXCR4。所有这些作用都可以在喂养期间使用β受体阻滞剂普萘洛尔逆转。这些发现表明，由交感神经系统驱动的血压升高可以影响调节造血系统的机制，从而促进动脉粥样硬化并导致心血管事件。
Hypertension is a major, independent risk factor for atherosclerotic cardiovascular disease. However, this pathology can arise through multiple pathways, which could influence vascular disease through distinct mechanisms. An overactive sympathetic nervous system is a dominant pathway that can precipitate in elevated blood pressure. We aimed to determine how the sympathetic nervous system directly promotes atherosclerosis in the setting of hypertension. We used a mouse model of sympathetic nervous system-driven hypertension on the atherosclerotic-prone apolipoprotein E-deficient background. When mice were placed on a western type diet for 16 weeks, we showed the evolution of unstable atherosclerotic lesions. Fortuitously, the changes in lesion composition were independent of endothelial dysfunction, allowing for the discovery of alternative mechanisms. With the use of flow cytometry and bone marrow imaging, we found that sympathetic activation caused deterioration of the hematopoietic stem and progenitor cell niche in the bone marrow, promoting the liberation of these cells into the circulation and extramedullary hematopoiesis in the spleen. Specifically, sympathetic activation reduced the abundance of key hematopoietic stem and progenitor cell niche cells, sinusoidal endothelial cells and osteoblasts. Additionally, sympathetic bone marrow activity prompted neutrophils to secrete proteases to cleave the hematopoietic stem and progenitor cell surface receptor CXCR4. All these effects could be reversed using the β-blocker propranolol during the feeding period. These findings suggest that elevated blood pressure driven by the sympathetic nervous system can influence mechanisms that modulate the hematopoietic system to promote atherosclerosis and contribute to cardiovascular events.
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影响因子：
4.9
作者：
Nakanishi, N;Sato, M;Tatara, K
通讯作者：
Tatara, K
外肺造血产生浸润动脉粥样硬化病变的LY-6C（高）单核细胞。
影响因子：
37.8
作者：
Robbins CS;Chudnovskiy A;Rauch PJ;Figueiredo JL;Iwamoto Y;Gorbatov R;Etzrodt M;Weber GF;Ueno T;van Rooijen N;Mulligan-Kehoe MJ;Libby P;Nahrendorf M;Pittet MJ;Weissleder R;Swirski FK
通讯作者：
Swirski FK
影响因子：
8.3
作者：
Davern, Pamela J.;Nguyen-Huu, Thu-Phuc;Head, Geoffrey A.
通讯作者：
Head, Geoffrey A.
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
39.3
作者：
Murphy, Andrew J.;Tall, Alan R.
通讯作者：
Tall, Alan R.