Low-Density Granulocytes Associate with Non-Calcified Coronary Plaque and Endothelial Damage in Psoriasis

Authors

• NJ Varghese
• HL Teague
• AK Dey
• A Joshi
• Y Baumer
• PK Dagur
• CL Harrington
• GE Sanda
• AD Belur
• A Goyal
• YA Elnabawi
• AV Sorokin
• DA Bluemke
• M Chen
• MP Playford
• JP McCoy
• Jr
• MJ Kaplan
• NN Mehta

Abstract

Chronic inflammation is increasingly recognized as a fundamental component of early cardiovascular disease (CVD). As a model of chronic inflammation we used psoriasis, a skin disease associated with increased susceptibility to CVD, to determine if a unique neutrophil subset, low-density granulocytes (LDGs), contributes to the early development of CVD. We assessed this in vivo by computed tomography and in vitro by induction of human aortic endothelial cell (HAoEC) damage. We characterized circulating LDG and normal-density granulocyte (NDG) frequencies in psoriatic and healthy patients, quantified NETosis in psoriatic LDGs and NDGs, and determined if psoriatic LDGs and NDGs are cytotoxic to HAoECs via a NETosis-specific mechanism. We demonstrate LDGs independently associate with non-calcified plaque in psoriasis, spontaneously form NETs, and induce HAoEC apoptosis, a NET-dependent effect. Our results identify a novel association of cardiovascular damage with the LDG subtype, gleaning insight into the causative role of LDGs in atherosclerotic plaque development and inflammatory atherogenesis. Future studies will focus on using RNA sequencing techniques to identify unique gene expression pathways pertinent to LDGs and NDGs.

Scientific Focus Area: Immunology

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