JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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Development of atherosclerotic plaques in a mouse model of pseudoxanthoma elasticum.

Acta Cardiologica 2014 December
OBJECTIVE: Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder, characterized by extensive mineralization of connective tissues and fragmentation of elastin fibres. PXE patients may sporadically suffer from severe cardiovascular complications caused by accelerated atherosclerosis. Consistent with this finding, recent evidence suggests that elastin fragmentation in arteries of atherosclerotic mice leads to unstable plaques and human-like complications such as myocardial infarction, stroke and sudden death. Because Abcc6-/- mice manifest the human features of PXE including the fragmentation of elastin fibres, Abcc6-/- mice were crossbred with ApoE-/- mice to investigate the level of plaque formation and potential complications.

METHODS AND RESULTS: ApoE-/- and ApoE-/- Abcc6-/- mice were fed a Western-type diet (WD) for 25 weeks to induce plaque formation.WD-fed animals showed neither signs of neurological dysfunction nor sudden death. Cardiac function of ApoE-/- Abcc6-/- mice, as assessed by echocardiography, was not different from ApoE-/- control mice. Histochemical analysis did not reveal elastin fragmentation or pronounced mineral deposition in the vessel wall. Plaques from the proximal ascending aorta and brachiocephalic artery of ApoE-/- Abcc6-/- mice were similar in size and composition as compared to ApoE-/- mice. Moreover, en face oil red O stainings of the aortic arch and descending thoracic aorta did not reveal enhanced plaque formation in ApoE-/- Abcc6-/- mice as compared to ApoE-/-controls.

CONCLUSION: ApoE-/-Abcc6-/- mice do not represent an adequate model of accelerated atherosclerosis and therefore are not useful to study atherosclerosis-related complications as observed in PXE patients.

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