Elevated serum levels of intercellular adhesion molecule ICAM-1 in Pseudoxanthoma elasticum

Hendig, Doris; Adam, Alexandra; Zarbock, Ralf; Szliska, Christiane; Kleesiek, Knut; Götting, Christian

doi:10.1016/j.cca.2008.04.002

Cited by 5 publications

(3 citation statements)

References 36 publications

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“…For example, the observations that Fetuin-A, MGP (Hendig et al, 2006, 2008b), vitamin K (Vanakker et al, 2010), osteogenic makers, and oxidative stress (Pasquali-Ronchetti et al, 2006; Garcia-Fernandez et al, 2008; Hendig et al, 2008a) are altered in the circulation of PXE patients points indirectly to unbalanced homeostasis of multiple organs and tissues. More direct evidence have shown the presence of pathological metabolite(s) in the serum of PXE patients and Abcc 6 −/− mice that promoted elastic fibers structural alterations and ectopic calcification (Le Saux et al, 2006; Jiang et al, 2007).…”

Section: The Molecular Characteristics Of Abcc6mentioning

confidence: 99%

The molecular and physiological roles of ABCC6: more than meets the eye

Saux¹,

Martin²,

Aherrahrou³

et al. 2012

Front. Gene.

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Abnormal mineralization occurs in the context of several common conditions, including advanced age, diabetes, hypercholesterolemia, chronic renal failure, and certain genetic conditions. Metabolic, mechanical, infectious, and inflammatory injuries promote ectopic mineralization through overlapping yet distinct molecular mechanisms of initiation and progression. The ABCC6 protein is an ATP-dependent transporter primarily found in the plasma membrane of hepatocytes. ABCC6 exports unknown substrates from the liver presumably for systemic circulation. ABCC6 deficiency is the primary cause for chronic and acute forms of ectopic mineralization described in diseases such as pseudoxanthoma elasticum (PXE), β-thalassemia, and generalized arterial calcification of infancy (GACI) in humans and dystrophic cardiac calcification (DCC) in mice. These pathologies are characterized by mineralization of cardiovascular, ocular, and dermal tissues. PXE and to an extent GACI are caused by inactivating ABCC6 mutations, whereas the mineralization associated with β-thalassemia patients derives from a liver-specific change in ABCC6 expression. DCC is an acquired phenotype resulting from cardiovascular insults (ischemic injury or hyperlipidemia) and secondary to ABCC6 insufficiency. Abcc6-deficient mice develop ectopic calcifications similar to both the human PXE and mouse DCC phenotypes. The precise molecular and cellular mechanism linking deficient hepatic ABCC6 function to distal ectopic mineral deposition is not understood and has captured the attention of many research groups. Our previously published work along with that of others show that ABCC6 influences other modulators of calcification and that it plays a much greater physiological role than originally thought.

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Section: The Molecular Characteristics Of Abcc6mentioning

confidence: 99%

The molecular and physiological roles of ABCC6: more than meets the eye

Saux¹,

Martin²,

Aherrahrou³

et al. 2012

Front. Gene.

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show abstract

“…Pseudoxanthoma elasticum (PXE), an autosomal-recessive disorder caused by mutations in the ATP binding cassette transporter gene ( ABCC6 ), is characterized by calcification and fragmentation of elastic fibers, proteoglycan accumulation in the extracellular matrix, skin lesions, and loss of visual acuity. 87 Hendig et al reported that in addition to having significantly higher serum ICAM-1 concentrations than healthy controls (303 vs 241 mg/L, P < 0.02), 49 PXE patients with two nonsense ABCC6 mutations or one nonsense mutation plus one missense mutation had significantly higher ICAM-1 concentrations than those lacking these mutations (314±16 vs 259±17 ng/mL, P < 0.03), but did not provide genotype-specific ICAM-1 concentrations in controls.…”

Section: Discussionmentioning

confidence: 99%

“…Published examples of gene-disease and gene-environment interactions were identified through keyword search on PubMed. Data from these studies were reanalyzed using genotype-specific means or medians presented in the original articles [44][45][46][47][48][49][50][51][52][53][54][55][56] or by extracting these values from published graphs [57][58][59][60][61][62] using the Microsoft PowerPoint formatting palette as previously described. 24 Specifically, histograms were created that display a precision medicine perspective of genotype-specific patient-control differences or treatment effects.…”

Section: Statisticsmentioning

confidence: 99%

Quantile-Specific Heritability of Inflammatory and Oxidative Stress Biomarkers Linked to Cardiovascular Disease

Williams¹

2022

JIR

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Purpose: Heritability (h 2 , the proportion of the phenotypic variance attributable to additive genetic effects) is traditionally assumed to be constant throughout the distribution of the phenotype. However, the heritabilities of circulating C-reactive protein, interleukin-6, plasminogen activator inhibitor type-1 (PAI-1), and monocyte chemoattractant protein-1 (MCP-1) concentrations depend upon whether the phenotype is high or low relative to their distributions (quantile-dependent expressivity), which may account for apparent gene-environment interactions. Whether the heritabilities of other inflammatory biomarkers linked to cardiovascular disease are quantile-dependent remain to be determined. Patients and Methods: Quantile-specific offspring-parent (β OP ) and full-sib regression slopes (β FS ) were estimated by applying quantile regression to the age-and sex-adjusted phenotypes of families surveyed as part of the Framingham Heart Study. Quantile-specific heritabilities were calculated as: h 2 =2β OP /(1+r spouse ) and h 2 ={(1+8r spouse β FS ) 0.5 -1}/(2r spouse ). Results: Heritability (h 2 ± SE) of lipoprotein-associated phospholipase A2 (Lp-PLA 2 ) mass concentrations increased from 0.11 ± 0.03 at the 10 th percentile, 0.08 ± 0.03 at the 25 th , 0.12 ± 0.03 at the 50 th , 0.20 ± 0.04 at the 75 th , and 0.26 ± 0.06 at the 90 th percentile, or 0.0023 ± 0.0006 per each one-percent increase in the phenotype distribution (P linear trend = 0.0004). Similarly, h 2 increased 0.0029 ± 0.0011 (P linear trend = 0.01) for sP-selectin, 0.0032 ± 0.0009 (P linear trend = 0.0001) for soluble intercellular adhesion molecule 1 (sICAM-1), and 0.0026 ± 0.0006 for tumor necrosis factor receptor 2 (TNFR2) (P linear trend = 5.0 × 10 −6 ) per each one-percent increase in their distributions when estimated from β OP . Osteoprotegerin and soluble ST2 heritability also increased significantly with increasing percentiles of their distributions when estimated from β FS . Lp-PLA 2 activity, CD40 ligand, TNFα, interleukin-18, and myeloperoxidase heritability showed no significant quantiledependence. Conclusion:The heritabilities of circulating Lp-PLA 2 -mass, sP-selectin, sICAM-1, TNFR2, osteoprotegerin and soluble ST2 concentrations are quantile-dependent, which may contribute to purported genetic modulations of: 1) sP-selectin's relationships to venous thrombosis, pulmonary hypertension, type 2 diabetes and atorvastatin treatment; 2) sICAM-I's relationships to brain abscess and atorvastatin treatment; and 3) Lp-PLA 2 's relationships to myocardial infarction and preeclampsia.

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Diseases of collagen and elastic tissue

Wang¹,

Lazar²

2012

McKee's Pathology of the Skin

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Elevated serum levels of intercellular adhesion molecule ICAM-1 in Pseudoxanthoma elasticum

Cited by 5 publications

References 36 publications

The molecular and physiological roles of ABCC6: more than meets the eye

The molecular and physiological roles of ABCC6: more than meets the eye

Quantile-Specific Heritability of Inflammatory and Oxidative Stress Biomarkers Linked to Cardiovascular Disease

Diseases of collagen and elastic tissue

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