Apremilast improves endothelial glycocalyx and microvascular perfusion: a possible protective mechanism against COVID-19

I Ikonomidis, G Pavlidis, J Thymis, P Rafouli-Stergiou, G Makavos, G Kostelli, P Katsimbri, V Lambadiari, J Parissis, E Kapniari, K Katogiannis, A Kountouri, E Korakas, K Theodoropoulos, E Papadavid
European Heart Journal 14 October 2021

Abstract

Background/Introduction

The phosphodiesterase 4 inhibitor apremilast is an approved treatment option for psoriasis.

Purpose

We aimed to investigate the effects of apremilast on endothelial glycocalyx, vascular and left ventricular (LV) myocardial function in psoriasis.

Methods

Ninety patients with psoriasis were randomized to receive apremilast (n=30), anti-tumor necrosis factor-a (etanercept, n=30), or cyclosporine treatment (n=30). At baseline and 4 months post-treatment, we measured: (1)Perfused boundary region (PBR) of the sublingual microvessels with a diameter 5–25μm using a dedicated camera (Sidestream Dark Field imaging, Microscan, Glycocheck). Increased PBR indicates reduced glycocalyx thickness. Perfused microvascular density (PMD), an index of microvascular perfusion, was also measured. (2)Pulse wave velocity (PWV – Complior; ALAM Medical) and central systolic blood pressure (cSBP), and (3)LV global longitudinal strain (GLS) and percent difference between peak twisting and untwisting at mitral valve opening (%dpTw-UtwMVO) using speckle-tracking echocardiography.

Results

Compared with baseline, PBR20–25 decreased only after apremilast treatment (−13% at 4 months, P<0.05) whereas no statistically significant changes in PBR20–25 were observed after etanercept or cyclosporine. Compared with etanercept and cyclosporine, apremilast resulted in a greater increase of PMD (+12% versus +3% versus +3%) and in a higher reduction of PWV (−10% versus −3% versus +8%) and cSBP (−8% versus −2% versus +7%) at 4 months. Apremilast showed a greater increase of GLS (+12% versus +5% versus +2%) and %dpTw-UtwMVO (+15% versus +3% versus +3%) than etanercept and cyclosporine (P<0.05 for all comparisons). Changes of PBR and PMD post-apremilast treatment correlated with a concomitant reduction of PWV and cSBP (P<0.05).

Conclusions

In psoriasis, apremilast confers a greater improvement of endothelial glycocalyx, microvascular perfusion and LV myocardial function compared with etanercept or cyclosporine treatment. Apremilast restores glycocalyx integrity and thus reduces vascular permeability to pro-inflammatory molecules. This may explain the beneficial effects of apremilast on COVID-19.