Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, China.
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, China.
J Nanosci Nanotechnol. 2019 Dec 1;19(12):7546-7550. doi: 10.1166/jnn.2019.16774.
Excessive -adrenergic stimulation induces cardiac fibrosis and inflammation and eventually leads to heart failure. It remains unclear whether the inflammatory factor and infiltration of macrophages are initiated from cardiac cells or the vascular system. We used 13-nm polyethylene glycol (PEG)-coated gold nanoparticles (GNPs) as size probes because they cannot penetrate normal vascular walls, and we found that over-stimulation of -adrenoceptors mediates cardiac inflammation and fibrosis by increasing vascular permeability. Stimulation with isoproterenol (ISO, a -adrenoceptor agonist) induced tissue-specific inflammatory infiltration and fibrosis in the hearts of mice. Consistent with these findings, 13-nm PEG-coated GNP as size probes were also observed to have tissue-specific targeting of the fibrotic heart, indicating over-stimulation of -adrenoceptors, increased vascular permeability in the heart, and initiated cardiac inflammation and fibrosis.
过度的肾上腺素能刺激会导致心脏纤维化和炎症，并最终导致心力衰竭。目前尚不清楚炎症因子和巨噬细胞浸润是从心脏细胞还是血管系统开始的。我们使用 13nm 聚乙二醇（PEG）包覆的金纳米颗粒（GNPs）作为尺寸探针，因为它们不能穿透正常的血管壁，我们发现，通过增加血管通透性，过度刺激β肾上腺素受体介导心脏炎症和纤维化。异丙肾上腺素（ISO，β肾上腺素受体激动剂）刺激诱导小鼠心脏的组织特异性炎症浸润和纤维化。与这些发现一致，我们还观察到 13nm PEG 包覆的 GNP 作为尺寸探针对纤维化心脏具有组织特异性靶向性，表明β肾上腺素受体过度刺激导致心脏血管通透性增加，并引发心脏炎症和纤维化。
