Neves Mario F, Endemann Dierk, Amiri Farhad, Virdis Agostino, Pu Qian, Rozen Rima, Schiffrin Ernesto L
Canadian Institutes of Health Research, Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7.
J Hypertens. 2004 May;22(5):959-66. doi: 10.1097/00004872-200405000-00018.
Elevated plasma homocysteine has been associated with cardiovascular disease, although a causal relationship is unclear. The purpose of this study was to evaluate whether mild hyperhomocysteinemia (H-Hcy) may increase vascular stiffness of small arteries.
Wild-type (+/+) and heterozygous (+/-) methylenetetrahydrofolate reductase (Mthfr) knockout mice, a new model of mild H-Hcy, were treated with vehicle or angiotensin (Ang) II infusion (400 ng/kg per min s.c.). Second-order mesenteric arteries were studied on pressurized myograph. They were exposed to intraluminal pressures ranging from 3 to 140 mmHg. Media thickness and lumen diameter were measured at each pressure level to determine wall mechanical properties. Collagen type I/III and elastin deposition in the vascular wall were evaluated by confocal immunofluorescence microscopy.
Media-to-lumen ratio was similar in Mthfr and Mthfr mice, and significantly increased by Ang II. The stress-strain relationship was shifted to the left in small mesenteric arteries from Mthfr compared to Mthfr mice, indicating that mild H-Hcy is associated with stiffer vessels. Ang II treatment in Mthfr mice enhanced the leftward shift in the stress-strain relationship and significantly increased the elastic modulus, suggesting the presence of stiffer wall components in small arteries in these animals. Increased collagen type I/III accumulation and decreased elastin content in the media of mesenteric arteries was noted in Mthfr compared to Mthfr mice. Ang II infusion augmented vascular collagen deposition in both groups, more substantially in Mthfr mice.
Mild hyperhomocysteinemia is associated with stiffer small arteries with increased collagen deposition in the media. These changes are accentuated by Ang II-induced blood pressure elevation.
血浆同型半胱氨酸水平升高与心血管疾病相关，但其因果关系尚不清楚。本研究旨在评估轻度高同型半胱氨酸血症（H-Hcy）是否会增加小动脉的血管僵硬度。
野生型（+/+）和杂合子（+/-）亚甲基四氢叶酸还原酶（Mthfr）基因敲除小鼠是轻度H-Hcy的新模型，分别给予赋形剂或皮下注射血管紧张素（Ang）II（400 ng/kg每分钟）处理。在压力肌动描记仪上研究二级肠系膜动脉。将它们暴露于3至140 mmHg的腔内压力下。在每个压力水平测量中膜厚度和管腔直径，以确定血管壁的力学特性。通过共聚焦免疫荧光显微镜评估血管壁中I/III型胶原蛋白和弹性蛋白的沉积。
Mthfr和Mthfr小鼠的中膜与管腔比值相似，Ang II使其显著增加。与Mthfr小鼠相比，Mthfr小鼠的小肠系膜小动脉的应力-应变关系向左移动，表明轻度H-Hcy与血管更僵硬有关。Mthfr小鼠接受Ang II治疗后，应力-应变关系进一步向左移动，弹性模量显著增加，表明这些动物的小动脉壁成分更僵硬。与Mthfr小鼠相比，Mthfr小鼠肠系膜动脉中膜的I/III型胶原蛋白积累增加，弹性蛋白含量减少。Ang II输注使两组的血管胶原蛋白沉积增加，在Mthfr小鼠中更明显。
轻度高同型半胱氨酸血症与小动脉僵硬有关，中膜胶原蛋白沉积增加。这些变化因Ang II诱导的血压升高而加剧。
