Development of atherosclerotic plaques in a mouse model of pseudoxanthoma elasticum

Abstract

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.

ABCC6 deficiency promotes dyslipidemia and atherosclerosis

“…The gradual decrease to undetectable levels of the small HDL fraction was notable (Supplemental Table 1). Because ABCC6 deficiency did not affect atherosclerosis development in mice with an ApoE −/− background as reported 30 , we specifically examined the plasma levels of this apolipoprotein in Abcc6 +/− ;Ldlr −/− and Abcc6 −/− ;Ldlr −/− mice, as it may have been a contributor to the enhanced atherosclerosis phenotype we observed. However, there was no significant variation as compared to Ldlr −/− controls (Supplemental Fig.…”

“…2. A recent study of ABCC6-deficient mice in ApoE −/− background showed no significant changes in atherosclerosis (or arterial calcification) as compared to ApoE −/− controls 30 . The results of this study are not necessarily discordant with ours and in fact provided some support to our overall conclusion regarding HDL.…”

Aesthetic complaints as clue to Pseudoxanthoma elasticum

“…The cardiovascular involvement, due to calcification of the internal elastic laminae of small and middle-sized arteries [1,[29][30][31], is characterized by intermittent claudication in the lower limbs and tiredness in the upper limbs, ischaemic brain infarction, angina pectoris, myocardial infarction, digestive angina, mitral prolapse, reno-vascular hypertension, gastrointestinal bleeding because of vasal fragility [1,22,[28][29][30][31][32]. Multiple asymptomatic calcifications on ultrasound examination in liver, spleen, breast, kidneys, testicles and pancreashave been reported in PXE [33,34].…”

A Systematic Review of Neurovascular Complications in Patients with Pseudoxanthoma Elasticum

“…5 Paradoxically, PXE patients are known to be at greater risk than the general population for coronary artery disease and peripheral artery disease, likely secondary to PXE-associated calcification and atherosclerosis. 6 Less commonly described in the literature are cerebrovascular complications resulting from PXE: ischemic infarction, intracranial aneurysm formation, and intracranial hemorrhage that can occur even in absence of aneurysm. Although these serious neurovascular events have the potential to result in permanent disability or death, current guidelines do not recommend prophylactic antiplatelet therapy for PXE patients due to the low incidence of these acute events and aforementioned risk of hemorrhage.…”