Lipke D W, McCarthy K J, Elton T S, Arcot S S, Oparil S, Couchman J R
Vascular Biology and Hypertension Program, University of Alabama at Birmingham.
Hypertension. 1993 Nov;22(5):743-53. doi: 10.1161/01.hyp.22.5.743.
A coarctation hypertensive rat model was used to examine the effects of elevated blood pressure on basement membrane component synthesis by cardiac myocytes and aorta using immunohistochemistry and Northern blot analysis. Carotid arterial pressure increased immediately on coarctation, and left ventricular hypertrophy was maximal within 5 days. In immunohistochemical studies, fibronectin and laminin were increased and the basement membrane chondroitin sulfate proteoglycan decreased in both the subendothelial space and smooth muscle cell basement membranes of the aorta above the clip compared with controls, whereas only fibronectin was elevated in the aorta below the clip. No change in basement membrane staining intensity for the cardiac myocytes was observed. Alterations in steady-state mRNA levels for fibronectin and laminin in the aorta paralleled those observed by immunohistochemical analysis with regard to protein and tissue type affected as well as intensity of the changes. However, changes in mRNA levels (but not protein deposition) for perlecan and type IV collagen were also observed in aortas from hypertensive rats compared with controls. Increases in steady-state mRNA levels for all basement membrane components in the heart and vasculature peaked before maximal cardiac hypertrophy (5 days). These studies indicate that alterations in basement membrane component deposition in the hypertrophied vasculature occur at both transcriptional and translational levels and suggest that the cell attachment glycoproteins fibronectin and laminin may be important factors in the vascular response to elevated transmural pressure.
采用缩窄性高血压大鼠模型,运用免疫组织化学和Northern印迹分析技术,研究血压升高对心肌细胞和主动脉基底膜成分合成的影响。缩窄术后颈动脉血压立即升高,左心室肥厚在5天内达到最大值。免疫组织化学研究显示,与对照组相比,缩窄部位上方主动脉的内皮下间隙和平滑肌细胞基底膜中的纤连蛋白和层粘连蛋白增加,基底膜硫酸软骨素蛋白聚糖减少,而缩窄部位下方主动脉中仅纤连蛋白升高。未观察到心肌细胞基底膜染色强度的变化。主动脉中纤连蛋白和层粘连蛋白的稳态mRNA水平变化与免疫组织化学分析观察到的蛋白质和组织类型变化以及变化强度一致。然而,与对照组相比,高血压大鼠主动脉中也观察到了基底膜蛋白聚糖和IV型胶原mRNA水平的变化(但蛋白质沉积无变化)。心脏和血管中所有基底膜成分的稳态mRNA水平在最大心肌肥厚(5天)之前达到峰值。这些研究表明,肥厚血管中基底膜成分沉积的改变发生在转录和翻译水平,提示细胞黏附糖蛋白纤连蛋白和层粘连蛋白可能是血管对跨壁压升高反应的重要因素。