The vascular phenotype in Pseudoxanthoma elasticum and related disorders: contribution of a genetic disease to the understanding of vascular calcification

Lefthériotis, Georges; Omarjee, Loukman; Saux, Olivier Le; Henrion, Didier; Ábrahám, Pierre; Prunier, Fabrice; Willoteaux, S.; Martin, Ludovic

doi:10.3389/fgene.2013.00004

Cited by 100 publications

(102 citation statements)

References 100 publications

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“…Intimal calcification is frequently associated with atherosclerosis, whereas calcification of the medial layers is frequently associated with aging or acquired metabolic diseases (such as diabetes and chronic renal insufficiency) and usually associated with arterial stiffening [3]. Arterial calcification has also been reported in young patients with a range of inherited monogenic diseases as a result of impaired regulation of soft tissue calcification [4]. Pseudoxanthoma elasticum (PXE; OMIM 264800, prevalence 1/25000 to 1/50000) is an autosomal recessive multisystem disease resulting from mutations in ABCC6 that encodes an ATP-binding cassette transporter mainly expressed in the liver and kidneys [5], [6].…”

Section: Introductionmentioning

confidence: 99%

The Contribution of Arterial Calcification to Peripheral Arterial Disease in Pseudoxanthoma Elasticum

et al. 2014

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Background and aimsThe contribution of arterial calcification (AC) in peripheral arterial disease (PAD) and arterial wall compressibility is a matter of debate. Pseudoxanthoma elasticum (PXE), an inherited metabolic disease due to ABCC6 gene mutations, combines elastic fiber fragmentation and calcification in various soft tissues including the arterial wall. Since AC is associated with PAD, a frequent complication of PXE, we sought to determine the role of AC in PAD and arterial wall compressibility in this group of patients.Methods and ResultsArterial compressibility and patency were determined by ankle-brachial pressure index (ABI) in a cohort of 71 PXE patients (mean age 48±SD 14 yrs, 45 women) and compared to 30 controls without PAD. Lower limb arterial calcification (LLAC) was determined by non-contrast enhanced helicoidal CT-scan. A calcification score (Ca-score) was computed for the femoral, popliteal and sub-popliteal artery segments of both legs. Forty patients with PXE had an ABI<0.90 and none had an ABI>1.40. LLAC increased with age, significantly more in PXE subjects than controls. A negative association was found between LLAC and ABI (r = −0.363, p = 0.002). The LLAC was independently associated with PXE and age, and ABI was not linked to cardiovascular risk factors.ConclusionsThe presence of AC was associated with PAD and PXE without affecting arterial compressibility. PAD in PXE patients is probably due to proximal obstructive lesions developing independently from cardiovascular risk factors.

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Section: Introductionmentioning

confidence: 99%

The Contribution of Arterial Calcification to Peripheral Arterial Disease in Pseudoxanthoma Elasticum

et al. 2014

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“…It is conceivable that elastic fiber mineralization and fragmentation in PXE arteries lead to an increase in arterial stiffness. 36 In addition, the presence of atherosclerotic plaques, which occur more frequently in PXE, is known to enhance stiffening of the arterial system. 37 Accordingly, we found a higher PWV in patients with PXE and carriers with PAD although this observation was not significant.…”

Section: Vascular Datamentioning

confidence: 99%

Characterization of Cardiovascular Involvement in Pseudoxanthoma Elasticum Families

Campens

Vanakker

Trachet

et al. 2013

ATVB

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Objective-Pseudoxanthoma elasticum (PXE) is an autosomal recessive connective tissue disorder with involvement of the skin, the retina, and the cardiovascular system. Cardiovascular involvement is mainly characterized by mineralization and fragmentation of elastic fibers of blood vessels and premature atherosclerosis. We conducted an ultrasound study to investigate the cardiovascular phenotype and to propose recommendations for the management of patients with PXE and heterozygous ABCC6 mutation carriers. Approach and Results-Thirty-two patients, 23 carriers, and 28 healthy volunteers underwent cardiac and vascular ultrasound studies. Cardiac imaging revealed left ventricular diastolic dysfunction in patients with PXE with a significantly prolonged deceleration time and lower septal early diastolic velocities of the mitral annulus compared with controls. Carriers also demonstrated significantly prolonged deceleration time. Carotid-to-femoral pulse wave velocity was significantly increased in patients with PXE when compared with carriers and controls. Vascular imaging revealed a high prevalence of peripheral artery disease in both patients and carriers and a significantly higher carotid intima-media thickness compared with controls. Conclusions-The results of this study clearly demonstrate impaired left ventricular diastolic function, impairment of the elastic properties of the aorta, and a high prevalence of peripheral artery disease in patients with PXE. Carriers also seem to exhibit a cardiovascular phenotype with mainly mild diastolic dysfunction and accelerated atherosclerosis. Increased awareness for cardiovascular events in both patients and heterozygous carriers is warranted. The ABCC6 gene (chrom. 16p13.1) codes for an ATPdependent transmembrane transporter, which is most abundant in the liver and kidney. Remarkably, the expression of the ABCC6 transporter in tissues clinically affected by PXE is very low. 19 This observation led to the hypothesis that PXE is primarily a metabolic disorder in which circulating serum factor(s) plays a role. 17 Another, and probably complimentary, pathogenetic mechanism is the so-called cellular hypothesis in which fibroblast perturbation may evoke local mineralization and elastic fiber alterations. This hypothesis is based on the observation that elastic fiber alterations are not present homogeneously throughout the skin and blood vessels of patients with PXE, but only in peculiar regions. Moreover, PXE skin fibroblasts exhibit a distinct behavior with altered biosynthetic expression profile and cell-cell and cell-matrix interactions compared with fibroblasts from normal subjects. [20][21][22] This study focuses on the cardiovascular phenotype of patients with PXE and carriers. Cardiovascular changes in patients with PXE are characterized by (1) mineralization and fragmentation of elastic fibers of the internal elastic lamina, medial and adventitial layers of medium-sized arteries and aorta, as well as of the endocardium, pericardium, connective tissue around vessels in t...

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“…Les patients sont fréquemment asymptomatiques [17,18]. D'autres atteintes sont retrouvées comme une Tableau 2 Critères diagnostiques pour le pseudoxanthome élastique (PXE).…”

Section: Le Pseudoxanthome éLastique (Pxe)unclassified

Artériopathies périphériques juvéniles

Cotard¹,

Nouni²,

Jaquinandi³

et al. 2016

Annales de Cardiologie et d'Angéiologie

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The vascular phenotype in Pseudoxanthoma elasticum and related disorders: contribution of a genetic disease to the understanding of vascular calcification

Cited by 100 publications

References 100 publications

The Contribution of Arterial Calcification to Peripheral Arterial Disease in Pseudoxanthoma Elasticum

The Contribution of Arterial Calcification to Peripheral Arterial Disease in Pseudoxanthoma Elasticum

Characterization of Cardiovascular Involvement in Pseudoxanthoma Elasticum Families

Artériopathies périphériques juvéniles

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