Nag S
Division of Neuropathology, University of Toronto, Canada.
J Neuropathol Exp Neurol. 1996 Mar;55(3):381-8. doi: 10.1097/00005072-199603000-00014.
Vascular hypertrophy or vascular remodeling are both associated with an increase in the extracellular matrix of cerebral arteries and arterioles in chronic hypertension. Rats with chronic renal hypertension were studied to determine whether the extracellular matrix proteins--collagen IV, laminin, and fibronectin--are increased in the thick-walled cerebral vessels in brain and those associated with areas of blood-brain barrier (BBB) breakdown to protein. The latter was detected by extravasation of endogenous serum proteins in brain. Serum proteins and the extracellular matrix proteins--fibronectin, laminin, and collagen IV--were detected by immunohistochemistry. Hypertensive rats having blood pressures over 150 mm Hg showed mild to moderate degrees of mural thickening of pial and intracerebral arterioles. In addition, these vessels demonstrated increased immunoreactivity with collagen IV, fibronectin, and laminin antisera. This occurred concomitant with the development of hypertension and prior to the observation of BBB breakdown to protein. Four rats having mean maximum systolic blood pressures in excess of 220 mm Hg developed multifocal areas of increased vascular permeability to endogenous serum proteins in the boundary zones of the territories supplied by the major cerebral arteries. The arterioles in these areas showed a severe degree of vascular thickening, which was due to medial hyperplasia/hypertrophy and increased mural deposition of serum proteins and the extracellular matrix proteins--laminin, fibronectin, and collagen IV. This study demonstrates that extracellular matrix proteins play an important role in the vascular response to increased intraluminal pressure. However, since this change occurs in diseases in the absence of hypertension it should be regarded as a nonspecific response of cellular components of vessel walls to injury.
血管肥大或血管重塑均与慢性高血压时脑动脉和小动脉细胞外基质的增加有关。对慢性肾性高血压大鼠进行研究，以确定细胞外基质蛋白——IV型胶原、层粘连蛋白和纤连蛋白——在脑内厚壁脑血管以及与血脑屏障（BBB）对蛋白质通透性增加区域相关的血管中是否增加。后者通过脑内内源性血清蛋白的外渗来检测。血清蛋白和细胞外基质蛋白——纤连蛋白、层粘连蛋白和IV型胶原——通过免疫组织化学检测。血压超过150 mmHg的高血压大鼠表现出软脑膜和脑内小动脉壁轻度至中度增厚。此外，这些血管对IV型胶原、纤连蛋白和层粘连蛋白抗血清的免疫反应性增加。这种情况与高血压的发展同时发生，且早于观察到BBB对蛋白质通透性增加之前。四只平均最大收缩压超过220 mmHg的大鼠在大脑主要动脉供血区域的边界区出现多灶性内源性血清蛋白血管通透性增加。这些区域的小动脉显示出严重的血管增厚，这是由于中膜增生/肥大以及血清蛋白和细胞外基质蛋白——层粘连蛋白、纤连蛋白和IV型胶原——在血管壁沉积增加所致。本研究表明，细胞外基质蛋白在血管对管腔内压力升高的反应中起重要作用。然而，由于这种变化也发生在无高血压的疾病中，因此应将其视为血管壁细胞成分对损伤的非特异性反应。
