Perivascular macrophages produce type I collagen around cerebral small vessels under prolonged hypertension in rats
Perivascular macrophages produce type I collagen around cerebral small vessels under prolonged hypertension in rats
复制标题
DOI：
10.1007/s00418-020-01948-9
复制
发表时间：
2021-01-04
影响因子：
2.3
通讯作者：
Ohno，Nobuhiko
中科院分区：
文献类型：
--
作者：
Inagaki，Takeshi;Fujiwara，Ken;Ohno，Nobuhiko
高血压导致脑血管结构重构，与脑血管病的病理生理密切相关。高血压下小动脉硬化的重塑和进展涉及纤维化沿着脑小动脉周围I型胶原的产生。然而，这种胶原蛋白产生的来源和调节机制仍然难以捉摸。在这项研究中，我们研究了血管周围巨噬细胞（PVM）是否参与高血压SHRSP/Izm大鼠脑小血管周围胶原的产生。12周龄高血压大鼠脑小血管周围I型胶原免疫反应性较4周龄高血压组和12周龄对照组有增高趋势。在超微结构分析中，使用透射电子显微镜，大量的胶原纤维的沉积可以观察到周围PVM附近的小动脉的长期高血压大鼠的细胞间隙。原位杂交分析显示，细胞的mRNA阳性的Col 1a 1，其中包括I型胶原，观察到大脑小血管附近。脑小血管周围的Col 1a 1阳性细胞与PVM的标记物CD 206共定位，但不与其他血管周围细胞如星形胶质细胞和血管平滑肌细胞的标记物胶质细胞酸性蛋白或结蛋白共定位。这些结果表明，I型胶原的生产增加，观察到周围的脑小血管高血压和Col 1a 1的PVM表达，并支持的概念，PVM参与高血压条件下的胶原生产和血管纤维化。
Hypertension leads to structural remodeling of cerebral blood vessels, which has been implicated in the pathophysiology of cerebrovascular diseases. The remodeling and progression of arteriolosclerosis under hypertension involve fibrosis along with the production of type I collagen around cerebral arterioles. However, the source and regulatory mechanisms of this collagen production remain elusive. In this study, we examined if perivascular macrophages (PVMs) are involved in collagen production around cerebral small vessels in hypertensive SHRSP/Izm rats. Immunoreactivity for type I collagen around cerebral small vessels in 12-week-old hypertensive rats tended to higher than those in 4-week-old hypertensive and 12-week-old control rats. In ultrastructural analyses using transmission electron microscopy, the substantial deposition of collagen fibers could be observed in the intercellular spaces around PVMs near the arterioles of rats with prolonged hypertension. In situ hybridization analyses revealed that cells positive for mRNA ofCol1a1, which comprises type I collagen, were observed near cerebral small vessels. TheCol1a1-positive cells around cerebral small vessels were colocalized with immunoreactivity for CD206, a marker for PVMs, but not with those for glial fibrillary acidic protein or desmin, markers for other perivascular cells such as astrocytes and vascular smooth muscle cells. These results demonstrated that enhanced production of type I collagen is observed around cerebral small vessels in rats with prolonged hypertension andCol1a1is expressed by PVMs, and support the concept that PVMs are involved in collagen production and vascular fibrosis under hypertensive conditions.