Measurement of Skin Desmosine as an Indicator of Altered Cutaneous Elastin in Draft Horses With Chronic Progressive Lymphedema

Cock, H. E V De; Affolter, Verena K.; Farver, Thomas B; Brantegem, Leen Van; Scheuch, Brad C.; Ferraro, Gregory L.

doi:10.1089/lrb.2006.4.67

Cited by 27 publications

(36 citation statements)

References 15 publications

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“…These fibrillin rich structures, which are part of a hierarchical fibrillar elastic apparatus (Gerli et al, 2000), are highly sensitive to interstitial stresses (Swartz and Skobe, 2001) and exert a significant tension on LECs: their main function is to widen the capillary lumen and open the overlapping cell junctions facilitating lymph formation (Cueni and Detmar, 2006). Abnormalities of AFs may reduce adsorption from interstitium and propulsion of lymph and cells and promote pathological conditions such as lymphedema or diseases related to impaired immune responses (De Cock et al, 2006). Dysfunctions may also be induced by extensive and chronic degradation of the ECM that renders lymphatic vessels non-responsive to the changes in the interstitium (Pelosi et al, 2007).…”

Section: Role Of Emilin1 Gc1q In Physiological and Pathological Condimentioning

confidence: 99%

The EMILIN/Multimerin Family

Colombatti¹,

Spessotto²,

Doliana³

et al. 2012

Front. Immun.

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Elastin microfibrillar interface proteins (EMILINs) and Multimerins (EMILIN1, EMILIN2, Multimerin1, and Multimerin2) constitute a four member family that in addition to the shared C-terminus gC1q domain typical of the gC1q/TNF superfamily members contain a N-terminus unique cysteine-rich EMI domain. These glycoproteins are homotrimeric and assemble into high molecular weight multimers. They are predominantly expressed in the extracellular matrix and contribute to several cellular functions in part associated with the gC1q domain and in part not yet assigned nor linked to other specific regions of the sequence. Among the latter is the control of arterial blood pressure, the inhibition of Bacillus anthracis cell cytotoxicity, the promotion of cell death, the proangiogenic function, and a role in platelet hemostasis. The focus of this review is to highlight the multiplicity of functions and domains of the EMILIN/Multimerin family with a particular emphasis on the regulatory role played by the ligand–receptor interactions of the gC1q domain. EMILIN1 is the most extensively studied member both from the structural and functional point of view. The structure of the gC1q of EMILIN1 solved by NMR highlights unique characteristics compared to other gC1q domains: it shows a marked decrease of the contact surface of the trimeric assembly and while conserving the jelly-roll topology with two β-sheets of antiparallel strands it presents a nine-stranded β-sandwich fold instead of the usual 10-stranded fold. This is likely due to the insertion of nine residues that disrupt the ordered strand organization and forma a highly dynamic protruding loop. In this loop the residue E933 is the site of interaction between gC1q and the α4β1 and α9β1 integrins, and contrary to integrin occupancy that usually upregulates cell growth, when gC1q is ligated by the integrin the cells reduce their proliferative activity.

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Section: Role Of Emilin1 Gc1q In Physiological and Pathological Condimentioning

confidence: 99%

The EMILIN/Multimerin Family

Colombatti¹,

Spessotto²,

Doliana³

et al. 2012

Front. Immun.

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“…Symptoms arise secondarily, most likely resulting from a reduced lymphatic drainage in skin and subcutis (De Cock et al . ). In scientific literature, both ‘CPL’ and ‘chronic pastern dermatitis’ (CPD) are used for this multifactorial and incurable disorder (Wallraf et al .…”

Section: Introductionmentioning

confidence: 97%

Genetic parameters for chronic progressive lymphedema in Belgian Draught Horses

Keyser

Janssens

Peeters

et al. 2014

J Animal Breeding Genetics

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Genetic parameters for chronic progressive lymphedema (CPL)-associated traits in Belgian Draught Horses were estimated, using a multitrait animal model. Clinical scores of CPL in the four limbs/horse (CPLclin ), skinfold thickness and hair samples (hair diameter) were studied. Due to CPLclin uncertainty in younger horses (progressive CPL character), a restricted data set (D_3+) was formed, excluding records from horses under 3 years from the complete data set (D_full). Age, gender, coat colour and limb hair pigmentation were included as fixed, permanent environment and date of recording as random effects. Higher CPLclin certainty (D_3+) increased heritability coefficients of, and genetic correlations between traits, with CPLclin heritabilities (SE) for the respective data sets: 0.11 (0.06) and 0.26 (0.05). A large proportion of the CPLclin variance was attributed to the permanent environmental effect in D_full, but less in D_3+. Date of recording explained a proportion of variance from 0.09 ± 0.03 to 0.61 ± 0.08. Additive genetic correlations between CPLclin and both skinfold thickness and hair diameter showed the latter two traits cannot be used as a direct diagnostic aid for CPL. Due to the relatively low heritability of CPLclin , selection should focus on estimated breeding values (from repeated clinical examinations) to reduce CPL occurrence in the Belgian Draught Horse.

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“…When interstitial fluid pressure increases, anchoring filaments exert tension on LECs, thereby widening the capillary lumen and opening the overlapping cell junctions, which enable fluid and macromolecule uptake and cell entry. It is thought that abnormalities of anchoring filaments may reduce adsorption from the interstitium and propulsion of lymph and cells and promote pathological conditions, such as lymphedema or diseases related to impaired immune responses (9,18). Furthermore, the perivascular ECM plays an integral role in lymphatic-vessel function, as the fluid equilibrium is controlled by the cooperation of both lymphatic function and the ECM (40).…”

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confidence: 99%

Emilin1 Deficiency Causes Structural and Functional Defects of Lymphatic Vasculature

Danussi

Spessotto

Petrucco

et al. 2008

Molecular and Cellular Biology

117

113

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Lymphatic-vasculature function critically depends on extracellular matrix (ECM) and on its connections with lymphatic endothelial cells (LECs). However, the composition and the architecture of ECM have not been fully taken into consideration in studying the biology and the pathology of the lymphatic system. EMILIN1, an elastic microfibril-associated protein, is highly expressed by LECs in vitro and colocalizes with lymphatic vessels in several mouse tissues. A comparative study between WT and Emilin1 ؊/؊ mice highlighted the fact that Emilin1 deficiency in both CD1 and C57BL/6 backgrounds results in hyperplasia, enlargement, and frequently an irregular pattern of superficial and visceral lymphatic vessels and in a significant reduction of anchoring filaments. Emilin1-deficient mice also develop larger lymphangiomas than WT mice. Lymphatic vascular morphological alterations are accompanied by functional defects, such as mild lymphedema, a highly significant drop in lymph drainage, and enhanced lymph leakage. Our findings demonstrate that EMILIN1 is involved in the regulation of the growth and in the maintenance of the integrity of lymphatic vessels, a fundamental requirement for efficient function. The phenotype displayed by Emilin1 ؊/؊ mice is the first abnormal lymphatic phenotype associated with the deficiency of an ECM protein and identifies EMILIN1 as a novel local regulator of lymphangiogenesis.Lymphatic and blood vascular systems have distinct structural characteristics that reflect their specific and complementary functions. The lymphatic vasculature represents a second circulatory system and maintains tissue fluid homeostasis; it plays a major role in the absorption of dietary fat and in immune response, transporting lymphocytes and antigen-presenting cells to regional lymph nodes; finally, it provides routes for tumor metastasis (8). The lymphatic system consists of a complex network of lymphatic capillaries, which are uniquely adapted for the uptake of protein-rich lymph from tissue interstitium, and collecting lymphatic vessels that transport lymph back to the blood vascular system. The latter are surrounded by a basement membrane and smooth muscle cells, which are less organized than in blood vessels and, in addition, have intraluminal valves, which prevent lymph backflow (26). By contrast, lymphatic capillaries are blind-end vessels, lined by a single thin layer of overlapping lymphatic endothelial cells (LECs) directly connected to the surrounding extracellular matrix (ECM) by means of anchoring elastic filaments (18). These structures play a fundamental role in lymphatic-vessel function and represent one of the main distinguishing features between lymphatic and blood capillaries. When interstitial fluid pressure increases, anchoring filaments exert tension on LECs, thereby widening the capillary lumen and opening the overlapping cell junctions, which enable fluid and macromolecule uptake and cell entry. It is thought that abnormalities of anchoring filaments may reduce adsorption from the intersti...

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Measurement of Skin Desmosine as an Indicator of Altered Cutaneous Elastin in Draft Horses With Chronic Progressive Lymphedema

Cited by 27 publications

References 15 publications

The EMILIN/Multimerin Family

The EMILIN/Multimerin Family

Genetic parameters for chronic progressive lymphedema in Belgian Draught Horses

Emilin1 Deficiency Causes Structural and Functional Defects of Lymphatic Vasculature

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