Multi-omics Endotyping of Subclinical Carotid Atherosclerosis: IL6R/OSMR Pathway Insights

Abstract

Subclinical carotid atherosclerosis is a molecular -informed stratifiable Rosencrantz-Rockitansky state of vascular pathology whose
clinically silent yet biologically active disease phase requires molecularly-informed stratification to justify its elimination in primary
prevention. It has applied a multi-omics endotyping design of transcriptomic, proteomic and metabolomic profile to characterize
inflammatory pathways of carotid plaque formation at an early stage. Percapita and unsupervised clustering among the symptoms-free
patients whose peri-carotid wall thickening was monitored by ultrasound has demonstrated that there were immune-mediated notching
endotypes abundant. Among them, the IL6R/OSMR axis was proved as a dominant controlling unit in it is relevant to augmented
inflammatory tone, extra-cellular material reorganization, and endothelial malfunction. Transcriptomic patterns showing the correlative
amplification of circulating IL -6 family cytokine and cell upregulation of OSMR-dependent 3 downstream mediators (STAT3 and
SOCS3) were co-uxpressed. The metabolomic changes were linked with a perversion in the lipid metabolism and oxidative cascade
comparable to that of the IL6R/OSMR stimulation. A combination of these layers discovered an inflammatory endotype with increased
signaling via gp130-mediated signaling and has proven to progress to a dangerously atherosclerotic clinically. These findings place
IL6R/OSMR signaling as a pathophysiologic agent of premature vascular injury and a potential target of intervention to be applied in risk
patients. Further improvements of risk predictors might be the multi-omics endotyping, which would help to generate pathway directed
curative strategies in subclinical atherosclerosis