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Lust et al. Vessel Plus 2021;5:7 Vessel Plus
DOI: 10.20517/2574-1209.2020.52

Original Article Open Access

Inhibition of cyclooxygenase activity by diclofenac
attenuates varicose remodeling of mouse veins

Leandra Lust , Hanna Kuk , Johanna Kohlhaas , Carsten Sticht , Thomas Korff 1,3
1
2
1
1
1 Institute of Physiology and Pathophysiology, Department of Cardiovascular Physiology, Heidelberg University, Heidelberg
69120, Germany.
2 Medical Clinic V, University Hospital Mannheim, Heidelberg University, Heidelberg, 69120, Germany.
3 European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Heidelberg 69120, Germany.
Correspondence to: Dr. Thomas Korff, Heidelberg University, Institute of Physiology and Pathophysiology, Department of
Cardiovascular Physiology, Im Neuenheimer Feld 326, Heidelberg 69120, Germany. E-mail: korff@physiologie.uni-heidelberg.de

How to cite this article: Lust L, Kuk H, Kohlhaas J, Sticht C, Korff T. Inhibition of cyclooxygenase activity by diclofenac attenuates
varicose remodeling of mouse veins. Vessel Plus 2021;5:7. http://dx.doi.org/10.20517/2574-1209.2020.52

Received: 22 Sep 2020 First Decision: 1 Dec 2020 Revised: 15 Dec 2020 Accepted: 7 Jan 2021 Published: 7 Feb 2021
Academic Editor: Rene Gordon Holzheimer Copy Editor: Xi-Jun Chen Production Editor: Jing Yu

Received: First Decision: Revised: Accepted: Published: x
Abstract
Science Editor: Copy Editor: Production Editor: Jing Yu Aim: The development of varicose veins is driven by risk factors that support the progression of venous
hypertension, specifically, by chronically augmenting the circumferential tension of the venous wall. We have
previously verified the relevance of this biomechanical stimulus for the activation of venous cells and the structural
remodeling of the vein wall. Recent transcriptome analyses revealed an increase in the expression of the gene
encoding prostaglandin-endoperoxide synthase 2 [cyclooxygenase 2 (COX-2)] in biomechanically stressed human
vein endothelial cells. This observation prompted us to investigate the functional relevance of COX activity for the
onset of pressure-induced venous remodeling.

Methods: For the in vitro experiments, isolated mouse veins were exposed to elevated intraluminal pressure levels
to study the markers of cellular activation. For the in vivo experiments, pressure-dependent varicose remodeling of
veins was induced by ligation of an efferent vein in the mouse auricle. Diclofenac was applied to inhibit the activity
of COX.

Results: Short-term exposure to elevated pressure levels stimulated the abundance of activated matrix-
metalloproteinase-2 (MMP-2) and mitogen activated protein kinase, ERK1/2, in isolated mouse veins, which was
inhibited upon treatment with diclofenac. Transdermal application of diclofenac-containing phospholipid-micelles
attenuated the corkscrew-like enlargement of veins and decreased the abundance of COX-2 and MMP-2 as well as
cell proliferation in the venous wall.

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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