Tissue remodelling and increased DNA damage in patients with incompetent valves in chronic venous insufficiency

慢性静脉功能不全患者的瓣膜功能不全导致组织重塑和 DNA 损伤增加

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作者:Miguel A Ortega, Oscar Fraile-Martínez, Cielo García-Montero, Leonel Pekarek, Miguel A Alvarez-Mon, Luis G Guijarro, Maria Del Carmen Boyano, Felipe Sainz, Melchor Álvarez-Mon, Julia Buján, Natalio García-Honduvilla, Ángel Asúnsolo

Abstract

Chronic venous insufficiency (CVI), in which blood return to the heart is impaired, is a prevalent condition worldwide. Valve incompetence is a complication of CVI that results in blood reflux, thereby aggravating venous hypertension. While CVI has a complex course and is known to produce alterations in the vein wall, the underlying pathological mechanisms remain unclear. This study examined the presence of DNA damage, pro-inflammatory cytokines and extracellular matrix remodelling in CVI-related valve incompetence. One hundred and ten patients with CVI were reviewed and divided into four groups according to age (<50 and ≥50 years) and a clinical diagnosis of venous reflux indicating venous system valve incompetence (R) (n = 81) or no reflux (NR) (n = 29). In vein specimens (greater saphenous vein) from each group, PARP, IL-17, COL-I, COL-III, MMP-2 and TIMP-2 expression levels were determined by RT-qPCR and immunohistochemistry. The younger patients with valve incompetence showed significantly higher PARP, IL-17, COL-I, COL-III, MMP-2 and reduced TIMP-2 expression levels and a higher COL-I/III ratio. Young CVI patients with venous reflux suffer chronic DNA damage, with consequences at both the local tissue and systemic levels, possibly associated with ageing.

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