Current Advances in the Pathogenesis of Varicose Veins

Naoum, Joseph J.; Hunter, Glenn C.; Woodside, Kenneth J.; Chen, Changyi

doi:10.1016/j.jss.2006.08.007

Cited by 47 publications

(68 citation statements)

References 36 publications

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“…In support of this view, VVs show valve hypertrophy, increased width of the valvular annulus (Corcos et al, 2000), decreased collagen content, and reduced viscoelasticity (Psaila and Melhuish, 1989), as well as increased monocyte and macrophage infiltration and inflammation in the valvular sinuses compared with distal VV walls (Ono et al, 1998). However, venous dilation and VVs are often seen below competent valves (Naoum et al, 2007). Also, increased collagen and decreased elastin have been demonstrated in both VVs and competent saphenous vein segments in proximity to varicosities, suggesting that ECM imbalance may occur in the vein wall prior to valve insufficiency (Gandhi et al, 1993).…”

Section: Matrix Metalloproteinases In Varicose Veinsmentioning

confidence: 96%

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: Matrix Metalloproteinases In Varicose Veinsmentioning

confidence: 96%

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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“…Vascular integrity in the healthy endothelium is maintained through the release of a variety of paracrine factors, such as NO. In venous disease, venous stasis in the microcirculation reduces the shear rate on the endothelial cells resulting in a reduction in cellular levels of NO (Naoum et al, 2007). This favours leucocyte adhesion and neutrophil and monocyte activation, which results in endothelial injury and dysfunction in lower-limb microvessels (Smith, 2006).…”

Section: Group Differences In Cutaneous Flux Responses Before Exercisementioning

confidence: 99%

“…Dilatation and incompetence of the deep, superficial, or perforating veins leads to impairment of the venous muscle pumps in the lower limb, often resulting in venous hypertension with upright posture (Naoum et al, 2007). Venous hypertension can activate neutrophils and monocytes, which can cause injury to the endothelium of lower-limb microvessels (Smith, 2006).…”

Section: Introductionmentioning

confidence: 99%

Impaired microvascular endothelial function is restored by acute lower-limb exercise in post-surgical varicose vein patients

Klonizakis

Tew

Michaels

et al. 2009

Microvascular Research

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“…The prevalence of varicose veins varies from 1% to 77% in different population groups, and the disease exerts a substantial effect on patient's quality of life [1,2]. Varicose veins are also associated with numerous complications, including thrombophlebitis.…”

Section: Introductionmentioning

confidence: 99%

“…Superficial thrombophlebitis results in a 3-fold increase in the risk of deep vein thrombosis (DVT) in patients with varicose veins, and the incidence of DVT in this population ranges from 6 to 30% [3]. Despite its great social impact, the primary cause of the disease has still not been clearly explained [2,5]. However, ample evidence implicates extensive extracellular matrix (ECM) remodeling and structural weakness of the vein wall as key factors in the pathogenesis of varicose veins [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Influence of thrombophlebitis on TGF-Î˛1 and its signaling pathway in the vein wall.

Kowalewski

Małkowski²,

Gacko³

et al. 2011

Folia Histochem Cytobiol.

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Extensive extracellular matrix remodeling of the vein wall is involved in varicose veins pathogenesis. This process is controlled by numerous factors, including peptide growth factors. The aim of the study was to evaluate influence of thrombophlebitis on TGF-β1 and its signaling pathway in the vein wall. TGF-β1 mRNA levels, growth factor content and its expression were evaluated by RT-PCR, ELISA, and western blot methods, respectively, in the walls of normal veins, varicose veins and varicose veins complicated by thrombophlebitis. Western blot analysis was used to assess TGF-β receptor type II (TGF-β RII) and p-Smad2/3 protein expression in the investigated material. Unchanged mRNA levels of TGF-β1, decreased TGF-β1 content, as well as decreased expression of latent and active forms of TGF-β1 were found in varicose veins. Increased expression of TGF-β RII and p-Smad2/3 were found in varicose veins. Thrombophlebitis led to increased protein expression of the TGF-β1 active form and p-Smad2/3 in the vein wall compared to varicose veins. TGF-β1 may play a role in the disease pathogenesis because of increased expression and activation of its receptor in the wall of varicose veins. Thrombophlebitis accelerates activation of TGF-β1 and activity of its receptor in the varicose vein wall.

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Current Advances in the Pathogenesis of Varicose Veins

Cited by 47 publications

References 36 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

Impaired microvascular endothelial function is restored by acute lower-limb exercise in post-surgical varicose vein patients

Influence of thrombophlebitis on TGF-Î˛1 and its signaling pathway in the vein wall.

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