Abstract 4145452: A platelet biosignature in psoriasis associates with enhanced cardiovascular risk

Introduction: Studies display an increased cardiovascular (CV) risk in psoriasis, but the underlying mechanisms and prevention strategies are not known. We investigated platelet aggregation and the platelet transcriptome as one potential mechanism to explain CV risk in psoriasis. Methods: Recruited psoriasis and controls (from the community) underwent platelet aggregation studies with light transmission aggregometry, and a subset underwent bulk platelet RNA sequencing with downstream analyses in R Studio. Results: Psoriasis subjects (n=75, age 47 ± 15 years, percent body surface area of psoriasis 6%) compared to controls (n=44, age 41 ± 15 years) were older ( p =0.02), overweight, (BMI [kg/m 2 ] 28 ± 6 vs. 26 ± 5, p <0.01), more often carried a diagnosis of dyslipidemia (35% vs. 16% p =0.03) and had higher high-sensitivity C-reactive protein values ([hsCRP in mg/L 3.1 ± 4.5 vs. 1.8 ± 2.5, p =0.02). Platelet aggregation was significantly higher in psoriasis vs. controls with collagen (86.6% vs. 72.0%, p =0.03) and ADP (88.2% vs. 75.7% vs. p =0.03). Platelet RNA sequencing revealed in psoriasis vs. control 384 genes upregulated and 414 genes downregulated ( p <0.05). Hierarchical clustering of the differentially expressed platelet RNA genes allowed a natural separation into three groups including one predominantly encompassing controls (18/20), a middle group (psoriasis = 24, controls = 20), and a third group of predominantly psoriasis (psoriasis = 25/26). Pathway analysis showed dysregulated TNF, interferon, and VEGF signaling pathways. Using penalized lasso regression, a psoriasis platelet RNA signature comprised of 400 differentially expressed platelet genes correlated with arterial stiffness ( r =0.3, p =0.02), coronary plaque ( r =0.5, p =0.02), and coronary calcium ( r =0.5, p =0.02) burden. Conclusion: Platelet aggregation is significantly increased in psoriasis with the platelet transcriptome associated with pro-inflammatory pathways and CV risk. Our results warrant further investigation of platelet involvement driving the heightened CV risk observed in psoriasis.