Apremilast Improves Endothelial Glycocalyx Integrity, Vascular and Left Ventricular Myocardial Function in Psoriasis

Ignatios Ikonomidis,Konstantinos Theodoropoulos,Evangelia Papadavid,Vaia Lambadiari,George Makavos,Nikolaos Kadoglou,Gavriella Kostelli,Irini Kapniari,George Pavlidis,Aikaterini Kountouri,Konstantinos Katogiannis,John Parissis,John Thymis,Pelagia Katsimbri

doi:10.3390/ph15020172

Ignatios Ikonomidis, Konstantinos Theodoropoulos + Show 12 more

Open Access

https://doi.org/10.3390/ph15020172

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Abstract

The phosphodiesterase 4 inhibitor apremilast is used for the treatment of psoriasis. We investigated the effects of apremilast on endothelial glycocalyx, vascular and left ventricular (LV) myocardial function in psoriasis. One hundred and fifty psoriatic patients were randomized to apremilast (n = 50), anti-tumor necrosis factor-α (etanercept; n = 50), or cyclosporine (n = 50). At baseline and 4 months post-treatment, we measured: (1) Perfused boundary region (PBR), a marker of glycocalyx integrity, in sublingual microvessels with diameter 5–25 μm using a Sidestream Dark Field camera (GlycoCheck). Increased PBR indicates damaged glycocalyx. Functional microvascular density, an index of microvascular perfusion, was also measured. (2) Pulse wave velocity (PWV-Complior) and (3) LV global longitudinal strain (GLS) using speckle-tracking echocardiography. Compared with baseline, PBR5–25 μm decreased only after apremilast (−12% at 4 months, p < 0.05) whereas no significant changes in PBR5–25 μm were observed after etanercept or cyclosporine treatment. Compared with etanercept and cyclosporine, apremilast resulted in a greater increase of functional microvascular density (+14% versus +1% versus −1%) and in a higher reduction of PWV. Apremilast showed a greater increase of GLS (+13.5% versus +7% versus +2%) than etanercept and cyclosporine (p < 0.05). In conclusion, apremilast restores glycocalyx integrity and confers a greater improvement of vascular and myocardial function compared with etanercept or cyclosporine after 4 months.

Highlights

Psoriasis is a chronic immune-mediated skin disease associated with increased prevalence of atherosclerosis, elevated coronary microcirculation dysfunction and impaired vascular and left ventricular (LV) myocardial function [1]
We have shown that Perfused boundary region (PBR), an accurate index of endothelial glycocalyx dimensions, together with functional microvascular density, are impaired in patients with psoriasis compared to healthy controls [22]
We have previously demonstrated that insulin resistance, as assessed by insulin sensitivity index and Matsuda index, was associated with PBR suggesting its detrimental effect on glycocalyx integrity [32]

Summary

Introduction

Psoriasis is a chronic immune-mediated skin disease associated with increased prevalence of atherosclerosis, elevated coronary microcirculation dysfunction and impaired vascular and left ventricular (LV) myocardial function [1]. Increased oxidative stress and inflammatory mediators including tumor necrosis factor (TNF)-α, interferon gamma (IFN-γ), Pharmaceuticals 2022, 15, 172. Endothelial glycocalyx is a complex mesh of sulfated proteoglycans, glycoproteins and associated glycosaminoglycans that covers the luminal side of vascular endothelial cells. It plays a pivotal role in vascular permeability by preventing the adhesion of leucocytes and platelets to the endothelium surface [4]. Pathophysiological conditions such as inflammation and increased oxidative stress are related to glycocalyx degradation resulting in endothelial dysfunction [5]. Damage of the glycocalyx integrity was proposed to promote early atherogenic processes [6,7,8] and is an independent and additive predictor to traditional risk factors for adverse outcome in subjects without overt cardiovascular disease [9]

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