Activated Platelets Induce Endothelial Cell Inflammatory Response in Psoriasis via COX-1

Abstract

Objective: Patients with psoriasis have impaired vascular health and increased cardiovascular disease (CVD). Platelets are key players in the pathogenesis of vascular dysfunction in cardiovascular disease and represent therapeutic targets in cardiovascular prevention. The object of this study was to define the platelet phenotype and effector cell properties on vascular health in psoriasis and evaluate whether aspirin modulates the platelet-induced phenotype. Approach and Results: Platelets from psoriasis patients (n=45) exhibited increased platelet activation (relative to age- and gender-matched controls, n=18), which correlated with psoriasis skin severity. Isolated platelets from psoriasis patients demonstrated a 2- to 3-fold ( P <0.01) increased adhesion to human aortic endothelial cells and induced proinflammatory transcriptional changes, including upregulation of IL 8 (interleukin 8), IL1β , and Cox (cyclooxygenase)-2 Platelet RNA sequencing revealed an interferon signature and elevated expression of COX-1 , which correlated with psoriasis disease severity ( r =0.83, P =0.01). In a randomized trial of patients with psoriasis, 2 weeks of 81 mg low-dose aspirin, a COX-1 inhibitor, reduced serum thromboxane (Tx) B 2 and reduced brachial vein endothelial proinflammatory transcript expression >70% compared with the no-treatment group ( P <0.01). Improvement in brachial vein endothelial cell inflammation significantly correlated with change in serum TxB 2 ( r =0.48, P =0.02). Conclusions: In patients with psoriasis, platelets are activated and induce endothelial cell inflammation. Low-dose aspirin improved endothelial cell health in psoriasis via platelet COX-1 inhibition. These data demonstrate a previously unappreciated role of platelets in psoriasis and endothelial cell inflammation and suggests that aspirin may be effective in improving vascular health in patients with psoriasis. Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT03228017.

National Psoriasis Foundation COVID-19 Task Force guidance for management of psoriatic disease during the pandemic: Version 2—Advances in psoriatic disease management, COVID-19 vaccines, and COVID-19 treatments

“…Patients with psoriasis are more prone to thrombosis and comorbidities that portend worse COVID-19 outcomes and may be more susceptible to infection, which raised concerns that they could be at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and worse COVID-19 outcomes. [4][5][6][7][8] Nevertheless, patients with psoriatic disease appear to have similar rates of infection with SARS-CoV-2 and COVID-19 outcomes as the general population, with multiple new studies from Italy, which primarily focused on patients with psoriasis receiving oral or biologic treatment, supporting our initial recommendation (guidance 1.1). [9][10][11] Additional new studies of patients with psoriatic arthritis (PsA) nested within cohorts of patients with rheumatic disease also suggest that they have similar rates of infection with SARS-CoV-2 and COVID-19 outcomes as the general population.…”

Associations of Platelet Count with Inflammation and Response to Anti-TNF-α Therapy in Patients with Ankylosing Spondylitis

“…Platelets have been recognized as crucial regulators of inflammatory processes under various pathophysiological conditions ( Karhausen et al, 2020 ). The inflammation caused by overactivated platelets can further promote the development of thrombosis, atherosclerosis, and cardiovascular diseases ( Barrett et al, 2019 ; Garshick et al, 2020 ; Schnorbus et al, 2020 ). Platelets exert critical roles in the development of inflammatory diseases such as inflammatory bowel disease (IBD) ( Chimen et al, 2019 ; Petrey et al, 2019 ; Nicolai and Massberg, 2020 ).…”

Proteolysis of Von Willebrand Factor Influences Inflammatory Endothelial Activation and Vascular Compliance in Atherosclerosis

“…In atherosclerosis, cytokine-mediated cell activation and expression of endothelial cell adhesion molecules contribute to the innate immune response ( 1 ). Platelet-endothelial interactions have also been shown to promote plaque development even at early stages of disease, most likely through proinflammatory effects of the platelet secretome, direct effects on macrophage subtype, or by serving as an alternative binding partner for leukocytes ( 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ). In vivo molecular imaging has recently been used to confirm histological findings that arterial platelet adhesion in atherosclerosis is mediated by increased endothelial-associated von Willebrand factor (vWF) and exposure of the vWF A1 binding domain for the glycoprotein-Ibα (GPIbα) subunit of the platelet GPIb-IX-V complex ( 10 , 11 , 12 ).…”