Mice with endothelial cell-selective adhesion molecule deficiency develop coronary microvascular rarefaction and left ventricle diastolic dysfunction.
Mice with endothelial cell-selective adhesion molecule deficiency develop coronary microvascular rarefaction and left ventricle diastolic dysfunction.
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DOI：
10.14814/phy2.15643
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发表时间：
2023-03
影响因子：
2.5
通讯作者：
中科院分区：
文献类型：
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内皮细胞选择性粘附分子（ESAM）调节炎性细胞粘附和迁移，促进血管生成。在此，我们研究了基础和血流动力学应激条件下ESAM在心脏血管化、炎性细胞浸润和左心室（LV）舒张功能中的作用。我们使用ESAM纯合基因缺失（ESAM−/−）小鼠，并进行单侧肾切除术和醛固酮输注（UNX‐Aldo）以诱导容量和压力超负荷。使用超声心动图，我们发现ESAM−/−小鼠的收缩功能没有变化。然而，他们发展LV舒张功能障碍，如由显著降低的E/A比率（E =早期，A =晚期二尖瓣流入峰值速度）、增加的E/e'比率、等容舒张时间（IVRT）和E波减速时间所指示的。冠状动脉血管的无偏自动追踪和3D重建显示，ESAM−/−小鼠的冠状动脉血管密度降低。ESAM−/−小鼠的动脉表现出受损的内皮发芽，并且在培养的内皮细胞中siRNA介导的ESAM敲低减少了管形成。ESAM−/−小鼠的变化伴随着心肌炎性细胞因子和髓过氧化物酶阳性中性粒细胞水平升高。此外，野生型小鼠的UNX‐Aldo程序诱导LV舒张功能障碍，伴有血清ESAM水平显著升高。与野生型相比，UNX‐Aldo的ESAM−/−小鼠显示LV舒张功能恶化，表现为IVRT增加和肺水肿。因此，我们认为ESAM在基础和血流动力学应激条件下，在适当的心肌血管化和维持LV舒张功能中起着机械作用。内皮细胞选择性粘附分子（ESAM）调节炎性细胞粘附和迁移，促进血管生成。我们认为ESAM缺乏的动物由于心肌血管密度降低、缺氧和炎症而发生左心室舒张功能障碍。血流动力学激发导致ESAM基因敲除小鼠左室舒张功能障碍加重。
Endothelial cell‐selective adhesion molecule (ESAM) regulates inflammatory cell adhesion and transmigration and promotes angiogenesis. Here, we examined the role of ESAM in cardiac vascularization, inflammatory cell infiltration, and left ventricle (LV) diastolic function under basal and hemodynamic stress conditions. We employed mice with homozygous genetic deletion of ESAM (ESAM−/−) and also performed uninephrectomy and aldosterone infusion (UNX‐Aldo) to induce volume and pressure overload. Using echocardiography, we found that ESAM−/− mice display no change in systolic function. However, they develop LV diastolic dysfunction, as indicated by a significantly reduced E/A ratio (E = early, A = late mitral inflow peak velocities), increased E/e’ ratio, isovolumic relaxation time (IVRT), and E wave deceleration time. An unbiased automated tracing and 3D reconstruction of coronary vasculature revealed that ESAM−/− mice had reduced coronary vascular density. Arteries of ESAM−/− mice exhibited impaired endothelial sprouting and in cultured endothelial cells siRNA‐mediated ESAM knockdown reduced tube formation. Changes in ESAM−/− mice were accompanied by elevated myocardial inflammatory cytokine and myeloperoxidase‐positive neutrophil levels. Furthermore, UNX‐Aldo procedure in wild type mice induced LV diastolic dysfunction, which was accompanied by significantly increased serum ESAM levels. When compared to wild types, ESAM−/− mice with UNX‐Aldo displayed worsening of LV diastolic function, as indicated by increased IVRT and pulmonary edema. Thus, we propose that ESAM plays a mechanistic role in proper myocardial vascularization and the maintenance of LV diastolic function under basal and hemodynamic stress conditions. Endothelial cell‐selective adhesion molecule (ESAM) regulates inflammatory cell adhesion and transmigration and promotes angiogenesis. We propose that animals deficient in ESAM develop left ventricular diastolic dysfunction due to reduced myocardial vascular density, hypoxia, and inflammation. Hemodynamic challenge lead to worsening of left ventricular diastolic dysfunction in ESAM knockout mice.
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DOI：
10.1152/ajpheart.00339.2017
发表时间：
2018-04-01
期刊：
American journal of physiology. Heart and circulatory physiology
影响因子：
--
作者：
Lindsey ML;Kassiri Z;Virag JAI;de Castro Brás LE;Scherrer-Crosbie M
通讯作者：
Scherrer-Crosbie M
影响因子：
9.7
作者：
Davila, Alec;Tian, Yanna;Bagi, Zsolt
通讯作者：
Bagi, Zsolt
影响因子：
4.8
作者：
Hirata, K;Ishida, T;Quertermous, T
通讯作者：
Quertermous, T
DOI：
10.1084/jem.20060565
发表时间：
2006-07-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Wegmann F;Petri B;Khandoga AG;Moser C;Khandoga A;Volkery S;Li H;Nasdala I;Brandau O;Fässler R;Butz S;Krombach F;Vestweber D
通讯作者：
Vestweber D
影响因子：
5.3
作者：
Park, Meyeon;Kulkarni, Ameya;Whooley, Mary
通讯作者：
Whooley, Mary