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

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.

Urinary liver‐type fatty acid binding protein is a biomarker reflecting renal damage and the ameliorative effect of drugs at an early stage of histone‐induced acute kidney injury

“…Recently, it was reported that PDE4 inhibitor improve vascular function, stabilize microcirculation, and improve myocardial function by restoring antiinflammatory effects and glycocalyx integrity in psoriasis patients. 18 In addition, it is expected a therapeutic effect on COVID-19 patients. 19 In experimental animal models of septic AKI in the previous study, a PDE4 inhibitor was administered before induction of sepsis from a prophylactic aspect.…”

“…PDE4 is an enzyme that hydrolyzes the second messenger cAMP to 5′‐AMP, which is widely distributed in inflammatory cells, central nervous system, smooth muscle, and kidney. Recently, it was reported that PDE4 inhibitor improve vascular function, stabilize microcirculation, and improve myocardial function by restoring anti‐inflammatory effects and glycocalyx integrity in psoriasis patients 18 . In addition, it is expected a therapeutic effect on COVID‐19 patients 19 .…”

“…1,2 Furthermore, we used rolipram, a phosphodiesterase 4 (PDE4) inhibitor known to have anti-inflammatory effects and it has protective effects on renal microcirculation and vascular function. [18][19][20] These drugs are also used or expected as therapeutic agents for infectious diseases such as COVID-19. 2,19,20 2 | MATERIALS AND METHODS…”

“…As a therapeutic agent, we used heparin, which has been reported to have a binding effect to histone through a charge interaction and protect the endothelial plasma membrane 1,2 . Furthermore, we used rolipram, a phosphodiesterase 4 (PDE4) inhibitor known to have anti‐inflammatory effects and it has protective effects on renal microcirculation and vascular function 18–20 . These drugs are also used or expected as therapeutic agents for infectious diseases such as COVID‐19 2,19,20 …”