Vascular Remodeling in Varicose Veins

Kockx, Mark; Knaapen, Michiel; Bortier, Hilde; Cromheeke, Kristel M.; Boutherin-Falson, Odile; Finet, M.

doi:10.1177/000331979804901101

Cited by 57 publications

(71 citation statements)

References 14 publications

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“…For instance, increased collagen content may compensate for decreased elastin levels at early stages of VVs, whereas collagen levels may decrease at later stages of the disease. This may explain the divergent reports regarding collagen content in VVs, where some studies showed a decrease (Haviarova et al, 1999), whereas other studies showed hardly any change (Venturi et al, 1996;Kockx et al, 1998) or even an increase (Gandhi et al, 1993).…”

Section: Mmps and Ecm Abnormalities In Vvsmentioning

confidence: 93%

“…In one study, active MMP-1 and total MMP-2 decreased, whereas total MMP-1 did not change in VVs (Gomez et al, 2014). Interestingly, measurements of collagen content in VV walls also showed variable results ranging from an increase (Gandhi et al, 1993) to no change (Kockx et al, 1998) to a decrease (Haviarova et al, 1999). The variability in MMP levels may be caused by examining VV segments from different regions, i.e., atrophic versus hypertrophic regions, or veins from patients at different stages of CVD, or failure to distinguish between pro-MMP and active forms of MMP.…”

Section: Mmp Levels In Vvsmentioning

confidence: 98%

“…Measurements of collagen content in VV walls have shown variable results ranging from an increase (Gandhi et al, 1993) to a decrease (Haviarova et al, 1999) or no change (Kockx et al, 1998). Both cultured dermal fibroblasts from patients with CVD and cultured VSMCs from VVs show increased synthesis of type I collagen but decreased synthesis of type III collagen, despite normal gene transcription, suggesting that VV patients may have a systemic abnormality in collagen production and post-translational inhibition of type III collagen synthesis in various tissues.…”

Section: Structural and Functional Abnormalities In Vvsmentioning

confidence: 99%

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Matrix Metalloproteinases as Regulators of Vein Structure and Function: Implications in Chronic Venous Disease

MacColl

Khalil

2015

J Pharmacol Exp Ther

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Lower-extremity veins have efficient wall structure and function and competent valves that permit upward movement of deoxygenated blood toward the heart against hydrostatic venous pressure. Matrix metalloproteinases (MMPs) play an important role in maintaining vein wall structure and function. MMPs are zinc-binding endopeptidases secreted as inactive pro-MMPs by fibroblasts, vascular smooth muscle (VSM), and leukocytes. ProMMPs are activated by various activators including other MMPs and proteinases. MMPs cause degradation of extracellular matrix (ECM) proteins such as collagen and elastin, and could have additional effects on the endothelium, as well as VSM cell migration, proliferation, Ca 21 signaling, and contraction. Increased lower-extremity hydrostatic venous pressure is thought to induce hypoxia-inducible factors and other MMP inducers/ activators such as extracellular matrix metalloproteinase inducer, prostanoids, chymase, and hormones, leading to increased MMP expression/activity, ECM degradation, VSM relaxation, and venous dilation. Leukocyte infiltration and inflammation of the vein wall cause further increases in MMPs, vein wall dilation, valve degradation, and different clinical stages of chronic venous disease (CVD), including varicose veins (VVs). VVs are characterized by ECM imbalance, incompetent valves, venous reflux, wall dilation, and tortuosity. VVs often show increased MMP levels, but may show no change or decreased levels, depending on the VV region (atrophic regions with little ECM versus hypertrophic regions with abundant ECM) and MMP form (inactive pro-MMP versus active MMP). Management of VVs includes compression stockings, venotonics, and surgical obliteration or removal. Because these approaches do not treat the causes of VVs, alternative methods are being developed. In addition to endogenous tissue inhibitors of MMPs, synthetic MMP inhibitors have been developed, and their effects in the treatment of VVs need to be examined.

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Section: Mmps and Ecm Abnormalities In Vvsmentioning

confidence: 93%

Section: Mmp Levels In Vvsmentioning

confidence: 98%

Section: Structural and Functional Abnormalities In Vvsmentioning

confidence: 99%

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Matrix Metalloproteinases as Regulators of Vein Structure and Function: Implications in Chronic Venous Disease

MacColl

Khalil

2015

J Pharmacol Exp Ther

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“…Susceptibility of the venous wall for stretching mainly depends on the smooth muscles and connective tissue fibres content in tunica media. It's known that intracellular matrix alterations of the venous wall is the cause of the development of CVD [11][12][13]. The property qualitative and quantitative composition of the intracellular matrix is the condition of the correctly building and integrality of the venous wall.…”

Section: Pathophysiologymentioning

confidence: 99%

The inflammatory reaction during chronic venous disease of lower limbs.

Ojdana

Safiejko²,

Lipska³

et al. 2009

Folia Histochem Cytobiol.

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Chronic venous disease (CVD) is an insufficiency of distal veins caused by their partial or total obstruction, endothelial distension and functional disorders. Chronic venous disease of lower limbs is common problem and affects millions of people. In this article we suggest that inflammatory process is involved in the structural remodeling in venous valves and in the venous wall, leading to valvular incompetence and the development of varicose veins.

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“…Numerous studies have investigated involvement of ECM molecules and enzyme inhibitors in varicose vein development. Defects in elastin metabolism [4], dysregulation of collagen synthesis and expression [12,13,14], abnormal collagen to elastin ratio and loss of the regular collagen/elastin lattice of the vein wall [13, 15] have been shown to be involved in the pathogenesis of varicose veins. Imbalance between tissue inhibitors of metalloproteinases (TIMP) and matrix metalloproteinase (MMP) production, in favor of an antiproteolytic activity, has also been described as a possible pathway to facilitate ECM accumulation in the diseased venous wall [16].…”

Section: Introductionmentioning

confidence: 99%

Identification of Differentially Expressed Genes in Human Varicose Veins: Involvement of Matrix Gla Protein in Extracellular Matrix Remodeling

et al. 2007

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This study was designed to identify the global pattern of differentially expressed genes in human varicose veins. Using suppressive subtractive hybridization, we identified overexpression of genes known to be associated with extracellular matrix remodeling, including collagen III, tissue inhibitor of metalloproteinases I, dermatopontin, matrix Gla protein (MGP) and tenascin C. Real-time polymerase chain reaction analysis confirmed the differential expression of these genes. The overexpression of MGP transcript was associated with increased MGP level in varicose veins, in particular the undercarboxylated form of the protein. Smooth muscle cells from varicose veins showed increased proliferation rate and enhanced matrix mineralization. This observation correlated with the presence of ectopic mineralization areas in the varicose vein walls. The use of warfarin, to inhibit MGP activity, or siRNA targeting MGP transcript induced a reduction in the exacerbated proliferation of varicose vein smooth muscle cells. Our results suggest that high expression of MGP in varicose veins may contribute to venous wall remodeling by affecting proliferation and mineralization processes probably through impaired carboxylation of MGP. In addition, suppressive subtractive hybridization results also produce a profile of differentially expressed genes in varicose veins, in particular extracellular matrix components. Further study of these genes will provide insights into their specific roles in the etiology of venous disease.

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Vascular Remodeling in Varicose Veins

Abstract: The present study describes

Cited by 57 publications

References 14 publications

Matrix Metalloproteinases as Regulators of Vein Structure and Function: Implications in Chronic Venous Disease

Matrix Metalloproteinases as Regulators of Vein Structure and Function: Implications in Chronic Venous Disease

The inflammatory reaction during chronic venous disease of lower limbs.

Identification of Differentially Expressed Genes in Human Varicose Veins: Involvement of Matrix Gla Protein in Extracellular Matrix Remodeling

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