Platelet Activation and a Platelet Biosignature Are Associated With Cardiovascular Risk in Patients With Controlled Psoriasis.

Background: The underlying mechanisms of atherosclerosis and strategies for identifying high cardiovascular risk in psoriasis are incompletely understood. Platelet activity is increased in psoriasis and induces vascular dysfunction. We investigated the platelet phenotype and platelet transcriptome as one potential mechanism to explain cardiovascular risk in psoriasis.

Tetraspanin CD37 regulates platelet hyperreactivity and thrombosis.

Aims: To investigate how psychosocial stress contributes to accelerated thrombosis, focusing on platelet activation and hyperreactivity. The specific objective was to identify novel platelet regulators involved in stress-mediated thrombosis, with a particular emphasis on the tetraspanin CD37.

Methods And Results: To explore how stress contributes to platelet hyperreactivity, platelets were isolated from (i) mice that experienced chronic variable stress and stress-free controls (n = 8/group) and (ii) human subjects with self-reported high- and no-stress levels (n = 18/group), followed by RNA-sequencing.

Burden of cardiometabolic risk factors and vascular health.

Background: Cardiometabolic risk factors diabetes, obesity, and hypertension are highly prevalent and contribute to increased cardiovascular disease (CVD). Endothelial dysfunction precedes CVD development. The current study aimed to investigate the EC transcriptome among individuals with varying degree of cardiometabolic risk.

An inflammatory transcriptomic signature in psoriasis associates with future cardiovascular events.

Background: Psoriasis is an inflammatory skin disease associated with increased cardiovascular (CV) risk, whose pathogenesis is not fully known.

Objective: We identified a transcriptomic signature in psoriasis and investigated its association with prevalent and future risk of a CV event to understand the connection between psoriasis and CV disease (CVD).

Methods: Psoriasis patients (n = 37) with a history of moderate-severe skin disease without CVD and 11 matched controls underwent whole blood RNA sequencing.

Statin therapy upregulates arachidonic acid status via enhanced endogenous synthesis in patients with plaque psoriasis.

Circulating fatty acids (FA) may be important in the psoriatic pro-inflammatory phenotype. FADS1 converts linoleic acid (LA) to arachidonic acid (AA), a precursor to potent signaling molecules. HMG-CoA reductase inhibitors (statins) increase FADS1/2 expression in vitro.

Role of plakophilin-2 expression on exercise-related progression of arrhythmogenic right ventricular cardiomyopathy: a translational study.

Aims: Exercise increases arrhythmia risk and cardiomyopathy progression in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients, but the mechanisms remain unknown. We investigated transcriptomic changes caused by endurance training in mice deficient in plakophilin-2 (PKP2cKO), a desmosomal protein important for intercalated disc formation, commonly mutated in ARVC and controls.

Methods And Results: Exercise alone caused transcriptional downregulation of genes coding intercalated disk proteins.

Platelets contribute to disease severity in COVID-19.

Objective: Heightened inflammation, dysregulated immunity, and thrombotic events are characteristic of hospitalized COVID-19 patients. Given that platelets are key regulators of thrombosis, inflammation, and immunity they represent prime candidates as mediators of COVID-19-associated pathogenesis. The objective of this study was to understand the contribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the platelet phenotype via phenotypic (activation, aggregation) and transcriptomic characterization.

Platelets amplify endotheliopathy in COVID-19.

Given the evidence for a hyperactive platelet phenotype in COVID-19, we investigated effector cell properties of COVID-19 platelets on endothelial cells (ECs). Integration of EC and platelet RNA sequencing revealed that platelet-released factors in COVID-19 promote an inflammatory hypercoagulable endotheliopathy. We identified and as transcripts enriched in COVID-19 platelets and were induced by megakaryocyte infection with SARS-CoV-2.

Chronic stress primes innate immune responses in mice and humans.

Psychological stress (PS) is associated with systemic inflammation and accelerates inflammatory disease progression (e.g., atherosclerosis).