A novel view to varicose veins pathogenesis: Proteomic profiling suggests a pivotal role of extracellular matrix degradation

Sigitas Urbonavicius; Reshaabi Srinanthalogen; Jes Sandermann; Mindaugas Valius; Algirdas Kaupinis; Maja Ludvigsen

doi:10.1177/02683555231206891

A novel view to varicose veins pathogenesis: Proteomic profiling suggests a pivotal role of extracellular matrix degradation

Sigitas Urbonavicius^*
, Reshaabi Srinanthalogen
, Jes Sandermann
, Mindaugas Valius
, Algirdas Kaupinis
, Maja Ludvigsen

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

1 Citation (Scopus)

Abstract

Introduction: Although morphological and anatomical studies indicate that venous wall weakening and subendothelial fibrosis characterize varicose veins (VV), the pathogenesis of VV remains poorly understood. The aim of this study is to obtain protein expression profiles in patients with VV and thereby get a step closer to understanding the pathogenesis of VV. Methods: Specimens were obtained from total of 10 patients, that is, from 5 patients undergoing VV surgical stripping and from 5 non-VV patients undergoing bypass surgery. Specimens were collected from the same layers of venous wall. Proteins were extracted from each specimen and analyzed by ion mobility spectrometry (IMS-MS). In total, 1387 were identified and 486 proteins were identified in all samples. From these, 15 proteins were differentially expressed between VV and non-VV samples (p <.05) and 12 of these showed a fold change >1.5. Results: Interestingly, among the differentially expressed proteins, only two proteins were significantly increased in the VV tissue, that is, GAPDH (p =.028, fold change 2.74), where several proteins involved in maintaining the homeostasis in the extracellular matrix, that is, the CXXC zinc finger protein 5 (CXXC5) and nucleoporin (SEH1) were prominently downregulated (p =.049, fold change 37.8, and p =.040, fold change 3.46). The downregulation in protein expression of CXXC5 and SEH1 as well as upregulation of GAPDH were validated by Western blotting. Conclusion: The identified differentially expressed proteins suggest an altered profile of the connective tissue proteins as well as an increased proteolytic enzyme activity which both may be central in the pathophysiology of varicose veins.

Original language	English
Journal	Phlebology
Volume	39
Issue	1
Pages (from-to)	20-28
Number of pages	9
ISSN	0268-3555
DOIs	https://doi.org/10.1177/02683555231206891
Publication status	Published - Feb 2024

Keywords

chronic venous insufficiency
pathology/histology
varicose veins
Extracellular Matrix/metabolism
Saphenous Vein/pathology
Transcription Factors/analysis
Humans
Proteomics
Varicose Veins/surgery
Vascular Surgical Procedures
DNA-Binding Proteins/analysis

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@article{61ec5072773b4ab998f0515afb69e15d,

title = "A novel view to varicose veins pathogenesis: Proteomic profiling suggests a pivotal role of extracellular matrix degradation",

abstract = "Introduction: Although morphological and anatomical studies indicate that venous wall weakening and subendothelial fibrosis characterize varicose veins (VV), the pathogenesis of VV remains poorly understood. The aim of this study is to obtain protein expression profiles in patients with VV and thereby get a step closer to understanding the pathogenesis of VV. Methods: Specimens were obtained from total of 10 patients, that is, from 5 patients undergoing VV surgical stripping and from 5 non-VV patients undergoing bypass surgery. Specimens were collected from the same layers of venous wall. Proteins were extracted from each specimen and analyzed by ion mobility spectrometry (IMS-MS). In total, 1387 were identified and 486 proteins were identified in all samples. From these, 15 proteins were differentially expressed between VV and non-VV samples (p <.05) and 12 of these showed a fold change >1.5. Results: Interestingly, among the differentially expressed proteins, only two proteins were significantly increased in the VV tissue, that is, GAPDH (p =.028, fold change 2.74), where several proteins involved in maintaining the homeostasis in the extracellular matrix, that is, the CXXC zinc finger protein 5 (CXXC5) and nucleoporin (SEH1) were prominently downregulated (p =.049, fold change 37.8, and p =.040, fold change 3.46). The downregulation in protein expression of CXXC5 and SEH1 as well as upregulation of GAPDH were validated by Western blotting. Conclusion: The identified differentially expressed proteins suggest an altered profile of the connective tissue proteins as well as an increased proteolytic enzyme activity which both may be central in the pathophysiology of varicose veins.",

keywords = "chronic venous insufficiency, pathology/histology, varicose veins, Extracellular Matrix/metabolism, Saphenous Vein/pathology, Transcription Factors/analysis, Humans, Proteomics, Varicose Veins/surgery, Vascular Surgical Procedures, DNA-Binding Proteins/analysis",

author = "Sigitas Urbonavicius and Reshaabi Srinanthalogen and Jes Sandermann and Mindaugas Valius and Algirdas Kaupinis and Maja Ludvigsen",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2023.",

year = "2024",

month = feb,

doi = "10.1177/02683555231206891",

language = "English",

volume = "39",

pages = "20--28",

journal = "Phlebology",

issn = "0268-3555",

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number = "1",

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A novel view to varicose veins pathogenesis: Proteomic profiling suggests a pivotal role of extracellular matrix degradation. / Urbonavicius, Sigitas; Srinanthalogen, Reshaabi; Sandermann, Jes et al.
In: Phlebology, Vol. 39, No. 1, 02.2024, p. 20-28.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - A novel view to varicose veins pathogenesis

T2 - Proteomic profiling suggests a pivotal role of extracellular matrix degradation

AU - Urbonavicius, Sigitas

AU - Srinanthalogen, Reshaabi

AU - Sandermann, Jes

AU - Valius, Mindaugas

AU - Kaupinis, Algirdas

AU - Ludvigsen, Maja

N1 - Publisher Copyright: © The Author(s) 2023.

PY - 2024/2

Y1 - 2024/2

N2 - Introduction: Although morphological and anatomical studies indicate that venous wall weakening and subendothelial fibrosis characterize varicose veins (VV), the pathogenesis of VV remains poorly understood. The aim of this study is to obtain protein expression profiles in patients with VV and thereby get a step closer to understanding the pathogenesis of VV. Methods: Specimens were obtained from total of 10 patients, that is, from 5 patients undergoing VV surgical stripping and from 5 non-VV patients undergoing bypass surgery. Specimens were collected from the same layers of venous wall. Proteins were extracted from each specimen and analyzed by ion mobility spectrometry (IMS-MS). In total, 1387 were identified and 486 proteins were identified in all samples. From these, 15 proteins were differentially expressed between VV and non-VV samples (p <.05) and 12 of these showed a fold change >1.5. Results: Interestingly, among the differentially expressed proteins, only two proteins were significantly increased in the VV tissue, that is, GAPDH (p =.028, fold change 2.74), where several proteins involved in maintaining the homeostasis in the extracellular matrix, that is, the CXXC zinc finger protein 5 (CXXC5) and nucleoporin (SEH1) were prominently downregulated (p =.049, fold change 37.8, and p =.040, fold change 3.46). The downregulation in protein expression of CXXC5 and SEH1 as well as upregulation of GAPDH were validated by Western blotting. Conclusion: The identified differentially expressed proteins suggest an altered profile of the connective tissue proteins as well as an increased proteolytic enzyme activity which both may be central in the pathophysiology of varicose veins.

AB - Introduction: Although morphological and anatomical studies indicate that venous wall weakening and subendothelial fibrosis characterize varicose veins (VV), the pathogenesis of VV remains poorly understood. The aim of this study is to obtain protein expression profiles in patients with VV and thereby get a step closer to understanding the pathogenesis of VV. Methods: Specimens were obtained from total of 10 patients, that is, from 5 patients undergoing VV surgical stripping and from 5 non-VV patients undergoing bypass surgery. Specimens were collected from the same layers of venous wall. Proteins were extracted from each specimen and analyzed by ion mobility spectrometry (IMS-MS). In total, 1387 were identified and 486 proteins were identified in all samples. From these, 15 proteins were differentially expressed between VV and non-VV samples (p <.05) and 12 of these showed a fold change >1.5. Results: Interestingly, among the differentially expressed proteins, only two proteins were significantly increased in the VV tissue, that is, GAPDH (p =.028, fold change 2.74), where several proteins involved in maintaining the homeostasis in the extracellular matrix, that is, the CXXC zinc finger protein 5 (CXXC5) and nucleoporin (SEH1) were prominently downregulated (p =.049, fold change 37.8, and p =.040, fold change 3.46). The downregulation in protein expression of CXXC5 and SEH1 as well as upregulation of GAPDH were validated by Western blotting. Conclusion: The identified differentially expressed proteins suggest an altered profile of the connective tissue proteins as well as an increased proteolytic enzyme activity which both may be central in the pathophysiology of varicose veins.

KW - chronic venous insufficiency

KW - pathology/histology

KW - varicose veins

KW - Extracellular Matrix/metabolism

KW - Saphenous Vein/pathology

KW - Transcription Factors/analysis

KW - Humans

KW - Proteomics

KW - Varicose Veins/surgery

KW - Vascular Surgical Procedures

KW - DNA-Binding Proteins/analysis

UR - https://www.scopus.com/pages/publications/85174179946

U2 - 10.1177/02683555231206891

DO - 10.1177/02683555231206891

M3 - Journal article

C2 - 37846077

AN - SCOPUS:85174179946

SN - 0268-3555

VL - 39

SP - 20

EP - 28

JO - Phlebology

JF - Phlebology

IS - 1

ER -

A novel view to varicose veins pathogenesis: Proteomic profiling suggests a pivotal role of extracellular matrix degradation

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