Computed tomography angiography in a patient with medial dibromuscular dysplasia

<p><b>Copyright information:</b></p><p>Taken from "Fibromuscular dysplasia"</p><p>http://www.OJRD.com/content/2/1/28</p><p>Orphanet Journal of Rare Diseases 2007;2():28-28.</p><p>Published online 7 Jun 2007</p><p>PMCID:PMC1899482.</p><p></p

Table_3_Assessment of arterial damage in vascular Ehlers-Danlos syndrome: A retrospective multicentric cohort.DOCX

BackgroundVascular Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder due to pathogenic variants in COL3A1 leading to medium-size-artery (MSA) dissection, aneurysm, rupture. Aortic lesions are rarer and less investigated. The objective was to describe the distribution of MSA and aortic lesions and the type of COL3A1 variants in a multicentric cohort of 330 adult vEDS patients.MethodsAt the time of the study, 87% were alive, 60.3% were index cases, and 60.0% were women. COL3A1 variants were identified using NGS and/or Sanger sequencing and classified according to functional consequences: 80.6% leading to dominant-negative (DN) and 19.4% leading to haploinsufficiency (HI). Imaging was systematically performed during the initial workup. Carotid mechanics were assessed by echo tracking in a subgroup of patients.ResultsArterial lesions were reported in 82.4% of the patients (N = 272): 83.5% had MSA lesions alone, 3.3% had aortic lesions alone, and 13.2% both. DN variants were associated with a higher prevalence of arterial lesions (P ConclusionThe prevalence of aortic lesions is not influenced by the COL3A1 genotype when adjusted for age. Patients with DN variant vEDS have a higher frequency of MSA lesions, especially in supra-aortic trunks associated with lower carotid stiffness. These results support optimized care and follow-up for these vulnerable patients.</p

Table_1_Assessment of arterial damage in vascular Ehlers-Danlos syndrome: A retrospective multicentric cohort.XLSX

BackgroundVascular Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder due to pathogenic variants in COL3A1 leading to medium-size-artery (MSA) dissection, aneurysm, rupture. Aortic lesions are rarer and less investigated. The objective was to describe the distribution of MSA and aortic lesions and the type of COL3A1 variants in a multicentric cohort of 330 adult vEDS patients.MethodsAt the time of the study, 87% were alive, 60.3% were index cases, and 60.0% were women. COL3A1 variants were identified using NGS and/or Sanger sequencing and classified according to functional consequences: 80.6% leading to dominant-negative (DN) and 19.4% leading to haploinsufficiency (HI). Imaging was systematically performed during the initial workup. Carotid mechanics were assessed by echo tracking in a subgroup of patients.ResultsArterial lesions were reported in 82.4% of the patients (N = 272): 83.5% had MSA lesions alone, 3.3% had aortic lesions alone, and 13.2% both. DN variants were associated with a higher prevalence of arterial lesions (P ConclusionThe prevalence of aortic lesions is not influenced by the COL3A1 genotype when adjusted for age. Patients with DN variant vEDS have a higher frequency of MSA lesions, especially in supra-aortic trunks associated with lower carotid stiffness. These results support optimized care and follow-up for these vulnerable patients.</p

Current progress in clinical, molecular, and genetic aspects of adult fibromuscular dysplasia

Fibromuscular dysplasia (FMD) is a non-atherosclerotic vascular disease that may involve medium-sized muscular arteries throughout the body. The majority of FMD patients are women. Although a variety of genetic, mechanical, and hormonal factors play a role in the pathogenesis of FMD, overall, its cause remains poorly understood. It is probable that the pathogenesis of FMD is linked to a combination of genetic and environmental factors. Extensive studies have correlated the arterial lesions of FMD to histopathological findings of arterial fibrosis, cellular hyperplasia, and distortion of the abnormal architecture of the arterial wall. More recently, the vascular phenotype of lesions associated with FMD has been expanded to include arterial aneurysms, dissections, and tortuosity. However, in the absence of a string-of-beads or focal stenosis, these lesions do not suffice to establish the diagnosis. While FMD most commonly involves renal and cerebrovascular arteries, involvement of most arteries throughout the body has been reported. Increasing evidence highlights that FMD is a systemic arterial disease and that subclinical alterations can be found in non-affected arterial segments. Recent significant progress in FMD-related research has led to improve our understanding of the disease’s clinical manifestations, natural history, epidemiology, and genetics. Ongoing work continues to focus on FMD genetics and proteomics, physiological effects of FMD on cardiovascular structure and function, and novel imaging modalities and blood-based biomarkers that can be used to identify subclinical FMD. It is also hoped that the next decade will bring the development of multi-centred and potentially international clinical trials to provide comparative effectiveness data to inform the optimal management of patients with FMD

Association between rs9349379 and artery thickness in healthy controls.

<p>Intima-media thickness and wall to lumen ratio are presented by genotype in all (A,D) women (B,E) and men (C,F) participants. We indicated p-values for the linear regression analyses under the additive model adjusted for age, sex and body surface area.</p

<i>phactr1</i> modulation in zebrafish affects vascular dimensions and patterning.

<p>Two-dimensional projections obtained from z-series confocal images in the trunk of control and phactr1 knockdown (KD) zebrafish embryos (two representative images per condition). Green represents the vascular endothelium as marked by EGFP. Greyscale represents the corresponding DIC bright field image of the fish trunk. DA: Dorsal aorta, SV: Segmental vessel, PCV: Posterior cardinal vein. Quantification of inner vascular diameter for the dorsal aorta (DA), posterior cardinal vein (PCV) and caudal artery (CA). (*) represents <i>P</i><0.05.</p

<i>PHACTR1</i> mRNA expression and immunostaining.

<p>(A) <i>PHACTR1</i> mRNA expression in human fibroblasts. <i>PHACTR1</i> mRNA levels were determined by RT-qPCR in cultured fibroblasts from controls (N = 39) and FMD cases (N = 51). <i>GAPDH</i> expression was used as control for normalization and data are expressed as mean fold change of <i>PHACTR1</i> relative to <i>GAPDH</i>. There is a non-significant trend toward overexpression of <i>PHACTR1</i> in FMD cases compared to controls (<i>P</i> = 0.61, Mann-Whitney test) whereas significant differences are uncovered after stratification by genotypes (<i>P</i> = 0.003, Kruskal-Wallis test). (B) Immunostaining of normal and FMD internal carotid using anti-PHACTR1 antibody. PHACTR1 was detected in endothelium and smooth muscle cells in the media. Staining is mostly cytoplasmic with regular alignment in normal carotids and typical disorganized cellular structure in media of FMD carotid.</p

Clinical features of the study populations.

<p>Clinical features of the study populations.</p

Variants associated with DCM.

<p>Variants associated with DCM.</p

Manhattan Plot of association P-values.

<p>95,499 variants were investigated for association with DCM by logistic regression analysis. Associations are summarized in a Manhattan plot (R/qqman package) which displays the eleven SNVs significantly associated with DCM (Q-values < 0.01) as green dots. Note that the applied logistic model assumed an additive mode of inheritance. For variants on chromosome 15 in the <i>ALPK3</i> region, a dominant mode of inheritance was better supported by the data (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172995#pone.0172995.t001" target="_blank">Table 1</a> for corresponding P-values)</p