Gene Expression Profiles in Varicose Veins Using Complementary DNA Microarray

Lee, Seokjong; Lee, Won-Chae; Choe, Yoonseok; Kim, Dowon; Na, Gunyeon; Kim, Jin Oh; Kim, Moonkyu; Kim, Jung‐Chul; Cho, Joonyong

doi:10.1111/j.1524-4725.2005.31103

Cited by 17 publications

(13 citation statements)

References 28 publications

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“…Complementary DNA (cDNA) microarrays comparing the differential gene expression of varicose and nonvaricose veins show an upregulation of 82 genes of the 3063 cDNA clones in varices. The upregulated genes include those of ECM molecules, cytoskeletal proteins and myofibroblasts such as transforming growth factor β-induced gene (BIGH3), tubulin, lumican, actinin, type I collagen, versican, actin and tropomyosin 49 . It has also been shown that three cDNAs similar to the L1M4 repeat sequence of clone RP11-57L9, clone RP11-299H13, and Alu repetitive sequence of human tropomycin 4 mRNA are expressed differently in varicose compared with nonvaricose veins 50 .…”

Section: Genes Regulating Vein Wall Structurementioning

confidence: 99%

Pathogenesis of primary varicose veins

Lim

Davies

2009

British Journal of Surgery

238

206

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Positive family history, age, sex and pregnancy are important risk factors for varicose vein formation. Areas of intimal hyperplasia and smooth muscle cell proliferation are often noted in varicose veins, although regions of atrophy are also present. The total elastin content in varicose as opposed to non-varicose veins is reduced; changes in overall collagen content are uncertain. Matrix metalloproteinases (MMPs), including MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9, and tissue inhibitor of metalloproteinase (TIMP) 1 and TIMP-3 are upregulated in varicose veins. Activation of the endothelium stimulates the recruitment of leucocytes and the release of growth factors, leading to smooth muscle cell proliferation and migration. Dysregulated apoptosis has also been demonstrated in varicose veins. An understanding of the pathophysiology of varicose veins is important in the identification of potential therapeutic targets and treatment strategies.

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Section: Genes Regulating Vein Wall Structurementioning

confidence: 99%

Pathogenesis of primary varicose veins

Lim

Davies

2009

British Journal of Surgery

238

206

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“…Also, patients with Klippel-Trenaunay syndrome often have VVs, supporting heritability of VVs (Delis et al, 2007). Other evidence for a genetic component of VVs include the following: a heterozygous mutation in the Notch3 gene identified in the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy pedigree with VVs (Saiki et al, 2006); a microarray analysis of 3063 human cDNAs from VVs showing upregulation of 82 genes, particularly those regulating ECM, cytoskeletal proteins, and myofibroblast production (Lee et al, 2005); individuals with Ehlers-Danlos syndrome type IV being prone to vascular pathology and VVs (Badauy et al, 2007); identification of single nucleotide polymorphisms in the promoter region of the MMP-9 gene among Chinese patients with VVs, with a 1562 C-to-T substitution associated with increased MMP-9 promoter activity and plasma levels (Xu et al, 2011); and the reduction of the elasticity of the lower-limb vein wall in children of VV patients (Reagan and Folse, 1971). …”

Section: Chronic Venous Diseasementioning

confidence: 99%

“…Family history and genetic and hereditary factors could also contribute to the risk for VVs (Lee et al, 2005). Primary lymphedema-distichiasis, a rare syndrome characterized by a mutation in the FOXC2 region of chromosome 16, is associated with VVs at an early age (Ng et al, 2005).…”

Section: Chronic Venous Diseasementioning

confidence: 99%

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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“…Важно отметить, что в ряде исследований [43] (информация по которым не представлена в табли-це) показали различия между варикозными и ин-тактными венами в экспрессии многих генов, в том числе структурных генов, регулирующих внеклеточ-ный матрикс, белки цитоскелета и миофибробла-сты. Однако остается неясным, является ли диффе-ренциальная экспрессия этих генов причиной или эффектом ВРВ [44].…”

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The Genetic Base of Chronic Venous Disease: a Review of Modern Concepts

Сметанина¹,

Shadrina²,

Золотухин³

et al. 2016

Flebol.

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Хронические заболевания вен (ХЗВ) нижних ко-нечностей представляют собой одно из наиболее часто встречающихся заболеваний сосудистой системы. Оценки распространенности варикозного расширения вен (ВРВ) варьируют в широких пределах: от 2 до 56% у мужчин и от 1 до 73% у женщин [1]. Различия в распро-страненности могут быть объяснены рядом факторов, в том числе методологией исследований. В целом, рас-пространенность выше в более развитых индустриаль-ных странах, чем в слаборазвитых регионах. 3 «новосибирский национальный исследовательский государственный университет», новосибирск, россия хронические заболевания вен нижних конечностей имеют классическую мультифакториальную этиологию, включающую в себя взаимодействие внешних факторов и особенностей структуры большого количества генов. несмотря на распростра-ненность этих заболеваний, наши знания об их патогенетических и молекулярных механизмах крайне скудны. В основе развития патологических процессов могут быть даже механические факторы, инициирующие сложный каскад клеточных реакций, которые впоследствии могут усиливаться генетическими факторами. гены, вовлеченные в первичную патологию вен, изучены недостаточно, и величину генетического вклада в фенотип заболевания еще предстоит прояснить. В насто-ящем обзоре уделено внимание генетическим составляющим таких состояний, как варикозная болезнь и хроническая венозная недостаточность, с отдельным обсуждением самого тяжелого клинического варианта -венозной трофической язвы. Во многих рассмотренных исследованиях в силу ряда причин предоставлены противоречивые данные о клинической значимости генетических ассоциаций. Прояснению связи генетических маркеров с разными патологическими составля-ющими хронических заболеваний вен будет способствовать проведение многоцентровых международных исследований, согласующихся по критериям включения и исключения пациентов и учитывающих этническую принадлежность анализи-руемых групп. настоящая работа является попыткой критического обзора и анализа литературы по ассоциативным гене-тическим исследованиям, касающимся варикозного расширения вен, хронической венозной недостаточности и венозной трофической язвы. кроме того, в ней обобщена и представлена в лаконичном виде информация, которая может быть полезна для клиницистов и в дальнейшем использована в современной флебологической практике. Chronic venous diseases of the lower extremities have classic multifactorial etiology including the interaction between the external factors and the structural features of a large number of genes. Despite the high prevalence of these diseases, our knowledge of the molecular mechanisms underlying their pathogenesis is extremely scarce. At the heart of the development of pathological processes, there may be even mechanical factors that trigger a complex cascade of cellular reactions that may subsequently be amplified by genetic factors. The genes involved in the primary venous pathology remain elusive and the magnitude of the genetic contribution to the disease phenotype is yet to be clarified. The current review i...

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Gene Expression Profiles in Varicose Veins Using Complementary DNA Microarray

Abstract: Many up-regulated genes were found in Ws by applying cDNA microarray. These gene profiles suggested a pathway associated with fibrosis and that wound healing might be related to the pathophysiology of VVs.

Cited by 17 publications

References 28 publications

Pathogenesis of primary varicose veins

Pathogenesis of primary varicose veins

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

The Genetic Base of Chronic Venous Disease: a Review of Modern Concepts

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