Chronic Venous Disease Patients Showed Altered Expression of IGF-1/PAPP-A/STC-2 Axis in the Vein Wall

Ortega, Miguel Á.; Fraile-Martínez, Óscar; Asúnsolo, Ángel; Martínez-Vivero, Clara; Pekarek, Leonel; Coca, Santiago; Guijarro, Luis; Álvarez‐Mon, Melchor; Buján, Julia; García‐Honduvilla, Natalio; Sáinz, Felipe

doi:10.1155/2020/6782659

Cited by 6 publications

(6 citation statements)

References 54 publications

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“…This evidence supports the importance of IGF-1/IGF-1R in the pathogenesis of CVeD. 30 IRS-4 may also negatively regulate the expression of other IRS-family proteins via competitive inhibition. 31 , 32 Thus, IRS-4 hyperactivation could be a downstream effect of IGF-1/IGF-1R binding that occurs in the venous wall of CVeD patients.…”

Section: Discussionsupporting

confidence: 78%

Chronic venous disease patients show increased IRS-4 expression in the great saphenous vein wall

et al. 2021

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Objectives Chronic venous disease (CVeD) is a multifactorial and debilitating condition that has a high prevalence in Western countries and an important associated socioeconomic burden. Varicose veins (VVs) are the most common manifestations of CVeD. Pathologically, many morphological and functional changes have been described in VVs, which most notably affect venous wall integrity. Previous studies have found several molecular alterations that negatively affect normal cell signaling pathways. Insulin receptor substrate (IRS)-4 is a central adaptor protein that is closely related to insulin/insulin-like growth factor-1 signaling upstream, phosphatidylinositol 3-kinase/Akt or mitogen-activated protein kinases downstream, and other proteins. These molecular pathways have been implicated in CVeD pathogenesis. Thus, the aim of our study was to identify the role of IRS-4 in VV tissue. Methods We conducted a histopathological study to analyze IRS-4 protein expression in CVeD patients compared with healthy controls. Results Our results demonstrate a significant increase in IRS-4 expression in VV tissue. Conclusions IRS-4 may be implicated in CVeD development and progression. Therefore, IRS-4 could be a potential diagnostic or therapeutic target for patients with this condition.

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Section: Discussionsupporting

confidence: 78%

Chronic venous disease patients show increased IRS-4 expression in the great saphenous vein wall

et al. 2021

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“…In this sense, significant changes in peptide growth factors and their receptors have been identified in the venous wall of patients with CVD, including acidic fibroblast growth factor (aFGF), VEGF, and insulin-like growth factor 1 (IGF-1), and its receptor (IGF-1R) [ 198 ]. The last route appears to be particularly important in the venous wall of patients with CVD, where we have recently reported an altered homeostatic IGF-1/PAPPA/STC-2 axis [ 199 ]. TGF-β1 has also been related to the pathophysiology of CVD.…”

Section: Pathophysiologymentioning

confidence: 99%

Understanding Chronic Venous Disease: A Critical Overview of Its Pathophysiology and Medical Management

Ortega

Fraile-Martínez

García-Montero

et al. 2021

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Chronic venous disease (CVD) is a multifactorial condition affecting an important percentage of the global population. It ranges from mild clinical signs, such as telangiectasias or reticular veins, to severe manifestations, such as venous ulcerations. However, varicose veins (VVs) are the most common manifestation of CVD. The explicit mechanisms of the disease are not well-understood. It seems that genetics and a plethora of environmental agents play an important role in the development and progression of CVD. The exposure to these factors leads to altered hemodynamics of the venous system, described as ambulatory venous hypertension, therefore promoting microcirculatory changes, inflammatory responses, hypoxia, venous wall remodeling, and epigenetic variations, even with important systemic implications. Thus, a proper clinical management of patients with CVD is essential to prevent potential harms of the disease, which also entails a significant loss of the quality of life in these individuals. Hence, the aim of the present review is to collect the current knowledge of CVD, including its epidemiology, etiology, and risk factors, but emphasizing the pathophysiology and medical care of these patients, including clinical manifestations, diagnosis, and treatments. Furthermore, future directions will also be covered in this work in order to provide potential fields to explore in the context of CVD.

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“…Panagiotou et al showed increased PAPP-A and STC-2 by exercise in healthy individuals [ 35 ]. Ortega et al demonstrated increased PAPP-A and decreased STC-2 gene expression in patients with chronic venous disease [ 36 ]. Hjortebjerg et al revealed unchanged PAPP-A and but decreased STC-2 expression after Roux-en-Y gastric bypass operation in obese subjects [ 37 ].…”

Section: Resultsmentioning

confidence: 99%

Preliminary investigation of gene expression levels of PAPP-A, STC-2, and HIF-1α in SARS-Cov-2 infected patients

et al. 2022

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Background Coronavirus-19 is still considered a pandemic that influences the world. Other molecular alterations should be clearer besides the increasing cytokine storm and pro-inflammatory molecules. Hypoxic conditions that induce HIF-1α lead to stimulate gene expression of STC-2 that targets PAPP-A expression. This study aimed to determine gene expression levels of PAPP-A, STC-2, and HIF-1α in COVID-19 infection. We also aimed to reveal the relationship of these genes with laboratory and clinical data of COVID-19 patients. Materials and Results We extracted RNA from peripheral blood samples of COVID-19(+) and COVID-19(−) individuals. The real-time PCR method was used to measure mRNA expression of PAPP-A, STC-2, and HIF-1α. Gene expression analysis was evaluated by the 2 −ΔΔCt method. PAPP-A, STC-2, and HIF-1α mRNA expressions of severe patients were higher than healthy individuals ( p = 0.0451 , p = 0.4466 , p < 0.0001, respectively). Correlation analysis of gene expression patterns of severe patients demonstrated a positive correlation between PAPP-A and STC-2 ( p < 0.0001 , r = 0.8638). Conclusion This is the first study that investigates the relation of PAPP-A, STC-2, and HIF-1α gene expression in patients with COVID-19 infection. Besides the routine laboratory findings, PAPP-A, STC-2, and HIF-1α mRNA expressions may be considered to patients’ prognosis as a sign of increased cytokines and pro-inflammatory molecules.

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Chronic Venous Disease Patients Showed Altered Expression of IGF-1/PAPP-A/STC-2 Axis in the Vein Wall

Cited by 6 publications

References 54 publications

Chronic venous disease patients show increased IRS-4 expression in the great saphenous vein wall

Chronic venous disease patients show increased IRS-4 expression in the great saphenous vein wall

Understanding Chronic Venous Disease: A Critical Overview of Its Pathophysiology and Medical Management

Preliminary investigation of gene expression levels of PAPP-A, STC-2, and HIF-1α in SARS-Cov-2 infected patients

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