Department of Anatomy, Division of Forensic Medicine, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
Department of Anatomy, Division of Histology and Cell Biology, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
Histochem Cell Biol. 2021 Apr;155(4):503-512. doi: 10.1007/s00418-020-01948-9. Epub 2021 Jan 4.
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 of Col1a1, which comprises type I collagen, were observed near cerebral small vessels. The Col1a1-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 and Col1a1 is expressed by PVMs, and support the concept that PVMs are involved in collagen production and vascular fibrosis under hypertensive conditions.
高血压导致脑血管结构重塑，这与脑血管疾病的病理生理学有关。高血压下小动脉粥样硬化的重塑和进展涉及纤维化以及脑小动脉周围 I 型胶原的产生。然而，这种胶原产生的来源和调节机制仍不清楚。在这项研究中，我们研究了高血压 SHRSP/Izm 大鼠的血管周围巨噬细胞（PVM）是否参与脑小血管周围的胶原产生。12 周龄高血压大鼠脑小血管周围 I 型胶原的免疫反应性趋于高于 4 周龄高血压大鼠和 12 周龄对照大鼠。在使用透射电子显微镜的超微结构分析中，在高血压持续时间延长的大鼠的小动脉附近 PVM 周围的细胞间隙中，可以观察到大量胶原纤维的沉积。原位杂交分析显示，在脑小血管附近，包含 I 型胶原的 Col1a1mRNA 阳性细胞被观察到。脑小血管周围 Col1a1 阳性细胞与 CD206 免疫反应性共定位，CD206 是 PVM 的标志物，但与胶质纤维酸性蛋白或结蛋白的免疫反应性不共定位，后者是星形胶质细胞和血管平滑肌细胞等其他血管周围细胞的标志物。这些结果表明，在高血压大鼠的脑小血管周围观察到 I 型胶原的产生增加，Col1a1 由 PVM 表达，并支持 PVM 参与高血压条件下的胶原产生和血管纤维化的概念。
