The mineralization of elastic fibers and alterations of extracellular matrix in pseudoxanthoma elasticum. Ultrastructure, immunocytochemistry, and X-ray analysis

Walker, E. R.

doi:10.1001/archderm.125.1.70

Cited by 23 publications

(21 citation statements)

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“…In PXE patients, compressibility tended to increase with age in young patients and to decrease in older ones. This observation is consistent with the pathogenesis of arterial lesions in PXE patients: PXE is characterized by an early accumulation of proteoglycans in large arteries, followed by calcifications at an older age, 18 which may attenuate fluid exchanges between blood, the arterial wall, and surrounding tissues. However, these results should be viewed with caution, because of the uneven distribution of CAW according to age.…”

Section: Compressibility In Pxe Patientssupporting

confidence: 87%

Compressibility of the Carotid Artery in Patients With Pseudoxanthoma Elasticum

et al. 2001

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Abstract-The arterial wall has generally been considered as noncompressible in in vitro studies. However, compressibility of the arterial wall (CAW) has never been studied in vivo in humans. Large interstitial proteoglycans play a major role in sustaining the compression generated by pulsatile forces. The aims of the present study were to develop an experimental methodology for the assessment of CAW in vivo in humans and to study CAW in patients with pseudoxanthoma elasticum (PXE), a genetic disease characterized by proteoglycan accumulation and fragmented, swollen, and calcified elastic fibers in connective tissues. We studied 19 female patients with PXE and 15 normal female control subjects matched for age and blood pressure. A high-resolution echo-tracking system was used for the continuous determination of internal diameter and wall thickness at the site of the common carotid artery. Matrices of the radiofrequency signal were analyzed with a dedicated software to measure carotid wall cross-sectional area every 4 milliseconds during 4 to 6 cardiac cycles. CAW was calculated as the stroke change in cross-sectional area. CAW was 44% higher in patients with PXE than in control subjects (6.8Ϯ2.6% versus 4.7Ϯ2.7%, respectively; PϽ0.05). In control subjects, CAW decreased with age in a linear manner (rϭϪ0.75, PϽ0.01). In PXE patients, the relationship with age was not homogeneous: CAW tended to increase with age before 40 years (Pϭ0.07) and significantly decreased with age in older patients (PϽ0.01). Carotid geometry and elastic properties did not differ between PXE patients and control subjects. In conclusion, CAW was measurable in vivo and noninvasively in humans. The higher CAW of PXE patients compared with that of control subjects suggests that proteoglycans are important determinants of compressibility.

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Section: Compressibility In Pxe Patientssupporting

confidence: 87%

Compressibility of the Carotid Artery in Patients With Pseudoxanthoma Elasticum

et al. 2001

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“…1C-E), appearing like a subtle craniosynostosis. However, this ectopic mineralization does not seem to occur in intercalvarial regions, but primarily in the adjacent dermis, as described for diseases such as pseudoxanthoma elasticum (PXE) (Apschner et al, 2014;Mackay et al, 2015;Walker et al, 1989). Indeed, both dermal fibroblasts and basal keratinocytes express col1a2 (Fig.…”

Section: Discussionmentioning

confidence: 80%

Retinoic acid-induced premature osteoblast-to-preosteocyte transitioning has multiple effects on calvarial development

Jeradi

Hammerschmidt

2016

Development

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We have previously shown that, in human and zebrafish, hypomorphic mutations of the gene encoding the retinoic acid (RA)-metabolizing enzyme Cyp26b1 result in coronal craniosynostosis, caused by an RA-induced premature transitioning of suture osteoblasts to preosteocytes, inducing ectopic mineralization of the suture's osteoid matrix. In addition, we showed that human CYP26B1 null patients have more severe and seemingly opposite skull defects, characterized by smaller and fragmented calvaria, but the cellular basis of these defects remained largely unclear. Here, by treating juvenile zebrafish with exogenous RA or a chemical Cyp26 inhibitor in the presence or absence of osteogenic cells or bone-resorbing osteoclasts, we demonstrate that both reduced calvarial size and calvarial fragmentation are also caused by RA-induced premature osteoblast-to-preosteocyte transitioning. During calvarial growth, the resulting osteoblast deprival leads to decreased osteoid production and thereby smaller and thinner calvaria, whereas calvarial fragmentation is caused by increased osteoclast stimulation through the gained preosteocytes. Together, our data demonstrate that RAinduced osteoblast-to-preosteocyte transitioning has multiple effects on developing bone in Cyp26b1 mutants, ranging from gain to loss of bone, depending on the allelic strength, the developmental stage and the cellular context.

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“…One hallmark of PXE is the coexistence in the affected and nonaffected skin of huge amounts of microfibrillar matter, corresponding to the accumulation of fragmented, swollen, and incomplete elastin fibers, together with various types of proteoglycans. [15][16][17] …”

Section: Discussionmentioning

confidence: 99%

“…29 In patients with PXE , elastic fibers in large arteries are abnormal and display fragmentations and calcifications. [15][16][17] These changes, similar to those occurring with aging, are expected to increase arterial stiffness. However, we observed no significant change in carotid distensibility in patients with PXE, suggesting that other mechanisms were involved.…”

Section: Interpretation Of Findingsmentioning

confidence: 99%

“…14 Histopathology of biopsies from clinically affected skin shows morphologically altered elastic fibers, which are fragmented and swollen and appear calcified when examined by special stains (eg, von Kossa), whereas PXE has also been characterized by proteoglycans accumulation, including heparan-sulfate and chondroitin-6-sulfate proteoglycans, glycosaminoglycan hyaluronic acid, decorin, and biglycan. [15][16][17] Despite identification of the genetic defect, little is known about the pathogenesis of vascular lesions in PXE and the means for preventing arterial complications in young adults.…”

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confidence: 99%

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Arterial Remodeling and Stiffness in Patients With Pseudoxanthoma Elasticum

Germain

Boutouyrie

Laloux

et al. 2003

ATVB

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Objective-Proteoglycans organize the extracellular matrix, act as signaling molecules, and are involved in cell migration and proliferation. They may play an important role in arterial geometric and elastic properties. The aim of the present study was to determine large artery phenotype in patients with pseudoxanthoma elasticum (PXE), a genetic disease characterized by proteoglycan accumulation and fragmented elastic fibers in connective tissues. Methods and Results-In 27 patients with PXE (25 females and 2 male) and 27 control subjects matched by age, sex, and blood pressure, we noninvasively determined the common carotid and radial artery diameter, intima-media thickness (IMT), and distensibility with high-definition echo-tracking systems and applanation tonometry. Patients with PXE had a significantly higher carotid IMT (611Ϯ106 versus 520Ϯ76 m, PϽ0.001) independently of body surface area, age, and mean blood pressure. The increase in carotid IMT predominated in older patients with PXE at the time of examination. No significant difference in carotid elastic properties was observed between patients with PXE and control subjects. At the site of the radial artery, distensibility was significantly higher in patients with PXE than in control subjects (11.6Ϯ11.

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The mineralization of elastic fibers and alterations of extracellular matrix in pseudoxanthoma elasticum. Ultrastructure, immunocytochemistry, and X-ray analysis

Cited by 23 publications

References 0 publications

Compressibility of the Carotid Artery in Patients With Pseudoxanthoma Elasticum

Compressibility of the Carotid Artery in Patients With Pseudoxanthoma Elasticum

Retinoic acid-induced premature osteoblast-to-preosteocyte transitioning has multiple effects on calvarial development

Arterial Remodeling and Stiffness in Patients With Pseudoxanthoma Elasticum

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