Protein Biomarkers in Blood Reflect the Interrelationships between Stroke Outcome, Inflammation, Coagulation, Adhesion, Senescence and Cancer

Abstract

The most important predictors for outcomes after ischemic stroke, that is, for health deterioration and death, are chronological age and stroke severity; gender, genetics and environmental factors also play a role. Of all these, only the latter can be influenced after the event, even though recurrent stroke may be prevented by antiaggregant/anticoagulant therapy, angioplasty of high-grade stenoses, and treatment of cardiovascular risk factors. Moreover, blood cell composition and protein biomarkers such as C-reactive protein or interleukins in serum/plasma are frequently considered as biomarkers of outcome, and they are connected to underlying molecular mechanisms such as inflammation, hypercoagulation, and cellular senescence. We surveyed protein biomarkers that were reported to be predictive for outcome after ischemic stroke, specifically considering biomarkers that predict long-term outcome (≥3 months) and that are measured over the first days following the event. We classified the protein biomarkers as immune‑inflammatory, coagulation-related, and adhesion-related biomarkers. Some of these biomarkers are closely related to cellular senescence and, in particular, to the inflammatory processes that can be triggered by senescent cells. Moreover, the processes that underlie inflammation, hypercoagulation and cellular senescence connect stroke to cancer, and biomarkers of cancer-associated thromboembolism, as well as of sarcopenia, overlap strongly with the biomarkers discussed here. Finally, we demonstrate that many of the outcome-predicting protein biomarkers form a close-meshed functional interaction network, suggesting that the outcome after stroke is partially determined by an interplay of the molecular processes relating to inflammation, coagulation, cell adhesion and cellular senescence.