Capillary injury in the ischemic brain of hyperlipidemic, apolipoprotein B-100 transgenic mice.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Süle
Zoltán
Z
Department of Anatomy, Faculty of Medicine, University of Szeged, Kossuth Lajos sgt. 40, H-6724 Szeged, Hungary.
Mracskó
Eva
E
Bereczki
Erika
E
Sántha
Miklós
M
Csont
Tamás
T
Ferdinandy
Péter
P
Bari
Ferenc
F
Farkas
Eszter
E
D000818:Animals; D053299:Apolipoprotein B-100 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications* / Q000601:surgery; D002196:Capillaries / Q000473:pathology* / Q000648:ultrastructure; D002791:Cholesterol, Dietary / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced / Q000150:complications; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008822:Mice, Transgenic
D053299:Apolipoprotein B-100; D002791:Cholesterol, Dietary; D008055:Lipids