Arterial Remodeling and Stiffness in Patients With Pseudoxanthoma Elasticum

Germain, Dominique P.; Boutouyrie, Pierre; Laloux, Brigitte; Laurent, Stéphane

doi:10.1161/01.atv.0000067428.19031.28

Cited by 44 publications

(44 citation statements)

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“…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.In accordance with Boutouyrie et al 38 and Germain et al, 39 we observed no significant decrease in CDC between the different groups, but rather a tendency toward a slower decrease of CDC in function of age in patients (Figure 2). The latter has already been reported by Kornet et al 9 In carriers we observed a similar trend.…”

supporting

confidence: 92%

“…In contrast, CDC measures stiffness at 1 point of the carotid artery. Further research is definitely warranted on the relation between alterations in wall composition and their relation to functional properties between the different parts of the arterial tree in patients with PXE.Carotid intima-media thickness was significantly increased in patients when compared with control subjects as also shown by Kornet et al 9 and Germain et al 39 Various mechanisms have been suggested to explain carotid wall thickening and thus higher carotid intima-media thickness in PXE subjects, including accelerated atherosclerosis, proteoglycan accumulation, and stimulation of vascular smooth muscle cell proliferation by increased proteoglycan content and elastin abnormalities.9,39 To our knowledge, there are no histological reports on vascular smooth muscle cell proliferation in patients with PXE. Our report is the first to show abnormal carotid intima-media thickness in carriers.…”

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confidence: 71%

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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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confidence: 92%

mentioning

confidence: 71%

Characterization of Cardiovascular Involvement in Pseudoxanthoma Elasticum Families

Campens

Vanakker

Trachet

et al. 2013

ATVB

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“…The second major difference was in elastin density, which decreased selectively in old males. Previous studies also have observed either decreased 33 or no change 39,40 in elastin with age, but some studies have observed elastin fragmentation, 21 as we did in this study.…”

Section: Discussioncontrasting

confidence: 63%

“…Although this possibility has not been studied in detail, it is less likely because variations in the content of proteoglycans in the vascular wall do not correlate with changes in vascular stiffness. 39,41,42 Another important parameter that might account for changes in aortic stiffness with aging was addressed in prior studies from our laboratory on the endothelial dysfunction that accompanies aging. 12,43 Related to this, soy proteins have been implicated in vascular and endothelial protection.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Gender-Specific Differences in Aortic Stiffness With Aging in Nonhuman Primates

et al. 2007

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Background-Our hypothesis was that the changes in vascular properties responsible for aortic stiffness with aging would be greater in old male monkeys than old female monkeys. Methods and Results-We analyzed the effects of gender differences in aging on in vivo measurements of aortic pressure and diameter and on extracellular matrix of the thoracic aorta in young adult (age, 6.6Ϯ0.5 years) versus old adult (age, 21.2Ϯ0.2 years) monkeys (Macaca fascicularis). Aortic stiffness, as represented by the pressure strain elastic modulus (Ep), increased more in old male monkeys (5.08Ϯ0.81; PϽ0.01) than in old females (3.06Ϯ0.52). In both genders, collagen density was maintained, collagen-bound glycation end products increased, and collagen type 1 decreased. However, elastin density decreased significantly (from 22Ϯ1.5% to 15Ϯ1.2%) with aging (PϽ0.05) only in males. Furthermore, only old males were characterized by a decrease (PϽ0.05) in collagen type 3 (an isoform that promotes elasticity) and an increase in collagen type 8 (an isoform that promotes the neointimal migration of vascular smooth muscle cells). In contrast to the data in monkeys, collagen types 1 and 3 both increased significantly in aging rats. Conclusions-There are major species differences in the effects of aging on aortic collagen types 1 and 3. Furthermore, because alterations in collagen density, collagen content, hydroxyproline, and collagen advanced glycation end products were similar in both old male and female monkeys, these factors cannot be responsible for the greater increase in stiffness in old males. However, changes in collagen isoforms and the decrease in elastin observed only in old males likely account for the greater increase in aortic stiffness. (Circulation. 2007;116:669-676.)

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“…function relationship of the arterial wall, and the effect on arterial stiffness of abnormal genetically determined wall components in particular. These diseases are complicated by major cardiovascular events, such as dilatation, dissection, and rupture (Marfan syndrome, Ehlers-Danlos syndrome) or hypertrophy and stenosis (Williams syndrome, pseudoxanthoma elasticum 38,39 ).…”

Section: Monogenic Disease and Related Knockout Micementioning

confidence: 99%

Structural and Genetic Bases of Arterial Stiffness

2005

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Abstract-Arterial stiffness has independent predictive value for cardiovascular events. We review data concerning the heritability of arterial stiffness, and propose an integrated view of the structural and genetic determinants of arterial stiffness, based on a candidate gene approach and recent studies on gene expression profile. Arterial stiffness seems to have a genetic component, which is largely independent of the influence of blood pressure and other cardiovascular risk factors. In animal models of essential hypertension (SHR and SHR-SP), structural modifications of the arterial wall include an increase in the number of elastin/smooth muscle cell (SMC) connections, and smaller fenestrations of the internal elastic lamina, possibly leading to redistribution of the mechanical load toward elastic materials. These modifications may give rise to mechanisms that explain why changes in arterial wall material accompanying wall hypertrophy in these animals are not associated with an increase in arterial stiffness. In monogenic connective tissue diseases (Marfan, Williams, and Ehlers-Danlos syndromes) and the corresponding animal models, precise characterization of the arterial phenotype makes it possible to determine the influence of abnormal genetically determined wall components on arterial stiffness. Such studies have highlighted the role of extracellular matrix signaling in the vascular wall and have shown that elastin and collagen not only display elasticity or rigidity but also are involved in the control of SMC function. These data provide strong evidence that arterial stiffness is affected by the amount and density of stiff wall material and the spatial organization of that material.

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Arterial Remodeling and Stiffness in Patients With Pseudoxanthoma Elasticum

Cited by 44 publications

References 45 publications

Characterization of Cardiovascular Involvement in Pseudoxanthoma Elasticum Families

Characterization of Cardiovascular Involvement in Pseudoxanthoma Elasticum Families

Mechanism of Gender-Specific Differences in Aortic Stiffness With Aging in Nonhuman Primates

Structural and Genetic Bases of Arterial Stiffness

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