Süle Zoltán, Mracskó Eva, Bereczki Erika, Sántha Miklós, Csont Tamás, Ferdinandy Péter, Bari Ferenc, Farkas Eszter
Department of Anatomy, Faculty of Medicine, University of Szeged, Kossuth Lajos sgt. 40, H-6724 Szeged, Hungary.
Life Sci. 2009 Jun 19;84(25-26):935-9. doi: 10.1016/j.lfs.2009.04.011. Epub 2009 May 3.
Apolipoprotein B-100 (apoB-100) has been implicated in hyperlipidemia, which contributes to the pathogenesis of vascular disorders. Our aim was to investigate whether the expression of human apoB-100 in transgenic mice and/or a high-cholesterol diet cause cerebral microvascular lesions, and whether these conditions augment ischemia-related capillary damage.
Human apoB-100 overexpressing transgenic (Tg(apoB-100), n=23) and wild-type mice (C5/B6, Wt, n=26) were supplied with standard or 2% cholesterol-enriched diet for 17-19 weeks. Cerebral ischemia was induced by unilateral common carotid artery occlusion. Cortical samples were embedded for electron microscopy. Microvascular density (number of microvascular profiles/examined area), lumen diameter, the swelling of astrocytic endfeet, the occurrence of endothelial microvilli (affected capillaries expressed as ratio of all capillaries encountered), and the ratio of intact capillaries (devoid of all the above pathology) were calculated.
The expression of apoB-100 coincided with decreased cortical microvascular density (195+/-7 vs. 223+/-8 vessels/mm(2), vs. Wt; P<0.008) and increased capillary lumen diameter (3.16+/-0.5 vs. 2.88+/-0.6 microm, vs. Wt; P<0.001). Cerebral ischemia promoted the swelling of perivascular astrocytes (62.1+/-4.2 vs. 36.5+/-4.0%, vs. contralateral, Wt; P<0.001), and reduced the ratio of intact capillaries (32.1+/-5.6 vs. 65.2+/-3.7%, vs. contralateral, Wt; P<0.001). Hyperlipidemia did not exacerbate the injury.
The overexpression of human apoB-100 alters the density of the microvascular network and the diameter of capillaries, which may compromise cerebrovascular reactivity during ischemia.
载脂蛋白B - 100（apoB - 100）与高脂血症有关，高脂血症会导致血管疾病的发病机制。我们的目的是研究人类apoB - 100在转基因小鼠中的表达和/或高胆固醇饮食是否会导致脑微血管病变，以及这些情况是否会加剧缺血相关的毛细血管损伤。
给过表达人类apoB - 100的转基因小鼠（Tg(apoB - 100)，n = 23）和野生型小鼠（C5/B6，Wt，n = 26）提供标准饮食或富含2%胆固醇的饮食，持续17 - 19周。通过单侧颈总动脉闭塞诱导脑缺血。将皮质样本包埋用于电子显微镜检查。计算微血管密度（微血管轮廓数量/检查面积）、管腔直径、星形胶质细胞终足肿胀、内皮微绒毛的出现情况（受影响的毛细血管表示为所遇到的所有毛细血管的比例）以及完整毛细血管的比例（无上述所有病理情况）。
apoB - 100的表达与皮质微血管密度降低（195±7对223±8个血管/mm²，对野生型；P < 0.008）和毛细血管管腔直径增加（3.16±0.5对2.88±0.6微米，对野生型；P < 0.001）同时出现。脑缺血促进了血管周围星形胶质细胞的肿胀（62.1±4.2对36.5±4.0%，对侧，野生型；P < 0.001），并降低了完整毛细血管的比例（32.1±5.6对65.2±3.7%，对侧，野生型；P < 0.001）。高脂血症并未加剧损伤。
人类apoB - 100的过表达改变了微血管网络的密度和毛细血管的直径，这可能会损害缺血期间的脑血管反应性。
