Elastic lamina defects are an early feature of aortic lesions in the apolipoprotein E knockout mouse.
The aortae from male apolipoprotein E knockout (apoE-/-) mice were examined by serial section immunohistochemistry and electron microscopy to determine the continuity of the internal elastic lamina (IEL) and its association with developing intimal lesions. While in this model, defects in the elastic laminae have previously been described beneath advanced xanthomatous lesions, this study demonstrates that disruption of the IEL may be a primary factor in the localization and pathogenesis of intimal lesions in the apoE-/- mouse. IEL defects were found beneath early lesions in animals as young as 8 weeks of age. Small defects without associated intimal alteration were also observed. The elastic tissue defects beneath early intimal lesions were usually transversely orientated with abrupt "break" edges. Regions consistent with direct enzymatic digestion of the IEL were relatively rare and only observed beneath advanced plaques, particularly in the brachiocephalic artery. The presence of IEL defects around branch sites of old C57BL/6J control mice along with their matching localization and morphology in apoE-/- appears consistent with biomechanical fatigue rather than direct enzymatic degradation. In conclusion, disruption of the IEL appears to be a prominent early, if not initial, feature of the apoE-/- model of atherosclerosis and may act as the nidus upon which intimal lesions develop.
Jones
Gregory T
GT
Department of Surgery, Otago Medical School, PO Box 913, Dunedin 9001, New Zealand. greg.jones@stonebow.atago.ac.nz
Jiang
Fan
F
McCormick
Sally P A
SP
Dusting
Gregory J
GJ
D000818:Animals; D001011:Aorta / Q000473:pathology; D001018:Aortic Diseases / Q000209:etiology* / Q000473:pathology*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology; D004547:Elastic Tissue / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D008854:Microscopy, Electron
D001057:Apolipoproteins E