Prado Cibele M, Rossi Marcos A
Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Int J Exp Pathol. 2006 Dec;87(6):425-36. doi: 10.1111/j.1365-2613.2006.00506.x.
The present study was carried out to investigate the role of hypertension in the genesis and localization of intimal lesions and medial remodelling found in the prestenotic segment in relation to a severe stenosis of the abdominal aorta just below the diaphragm. Male young rats were divided randomly into operated group, animals submitted to surgical abdominal aorta stenosis, and sham-operated group, a control group of animals submitted to sham operation to simulate abdominal aorta stenosis. Aortas in the hypertensive prestenotic segment with increased circumferential wall tension associated with normal tensile stress, laminar flow/normal wall shear stress were characterized by enlarged heterogeneous endothelial cells elongated in the direction of the blood flow, diffusely distributed conspicuous neointimal plaques and medial thickening. The immunohistochemical analysis revealed an increased expression of eNOS, iNOS, nitrotyrosine and transforming growth factor-beta (TGF-beta) in endothelial cells and/or smooth muscle cells in this segment. Our findings suggest that increased circumferential wall tension due to hypertension plays a pivotal role in the remodelling of the prestenotic segment through biomechanical effects on oxidative stress and increased TGF-beta expression. Further studies are needed to clarify the intrinsic pathogenetic mechanism of focal distribution of the neointimal plaques in the hypertensive segment.
本研究旨在探讨高血压在与膈下腹主动脉严重狭窄相关的狭窄前节段内膜病变形成和定位以及中膜重塑中的作用。雄性幼鼠被随机分为手术组(接受腹主动脉狭窄手术的动物)和假手术组(接受假手术以模拟腹主动脉狭窄的动物对照组)。高血压狭窄前节段的主动脉,其周向壁张力增加,拉伸应力正常,血流层流/壁面切应力正常,其特征为内皮细胞增大且形态各异,沿血流方向拉长,有弥漫分布的明显新生内膜斑块和中膜增厚。免疫组织化学分析显示,该节段内皮细胞和/或平滑肌细胞中内皮型一氧化氮合酶(eNOS)、诱导型一氧化氮合酶(iNOS)、硝基酪氨酸和转化生长因子-β(TGF-β)的表达增加。我们的研究结果表明,高血压导致的周向壁张力增加通过对氧化应激和TGF-β表达增加的生物力学作用,在狭窄前节段的重塑中起关键作用。需要进一步研究来阐明高血压节段新生内膜斑块局灶分布的内在发病机制。