# From Vascular Dysfunction to Atherothrombosis: The Pivotal Role of Eicosanoids and Their Receptors in Platelet and Endothelial Imbalance: A Scoping Review

## TL;DR

This review explores how eicosanoids and their receptors contribute to vascular and platelet dysfunction in atherothrombosis, suggesting new therapeutic targets for cardiovascular diseases.

## Contribution

The paper highlights the role of eicosanoids, particularly PGE2 and its receptors, as potential therapeutic targets for atherothrombosis.

## Key findings

- Eicosanoids like PGE2 play a key role in atherosclerosis through EP receptor signaling.
- Pharmacological modulation of eicosanoid receptors may offer new treatments for cardiovascular dysfunction.
- Current evidence is limited, requiring further in vitro, in vivo, and clinical studies for validation.

## Abstract

Vascular endothelium balances antithrombotic and anti-inflammatory activity to control blood vessel tone under physiological conditions. However, endothelial dysfunction impairs these processes, causing a state that promotes clotting and inflammation. Eicosanoids are a major class of bioactive lipid mediators crucial for modulating endothelial and platelet function. Research has highlighted the roles of eicosanoids in vascular diseases, showing pro-inflammatory, prothrombotic, and protective activities. Specifically, prostaglandin E2 (PGE2) is crucial because of its major role in atherosclerosis development and progression, acting via EP receptors involved in forming, maintaining, and stabilizing atherosclerotic lesions, thereby making PGE2-EP signalling a specific target for treating cardiovascular diseases. This review will explore the evidence on eicosanoids and the role of their receptor modulation in platelet and vascular dysfunction in atherothrombosis. The studies included in this scoping review were retrieved from PubMed, Web of Science, Cochrane, and Scopus in accordance with the Preferred Reporting Items for Scoping Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) statement and the Population Intervention Comparison Outcome Population (PICO) framework. Eight clinical studies were found, which highlighted the crucial role of eicosanoids, like prostaglandins and their receptors, in endothelial and platelet dysfunction, and also how pharmacological mechanisms affect atherothrombosis. A new therapeutic approach for cardiovascular dysfunction is indicated by the recent findings, specifically against atherothrombosis, focusing on eicosanoids, their receptors, and processes like oxidative stress. Despite this evidence, there is a lack of comprehensive research results from scientific databases; therefore, further in vitro, in vivo, and clinical studies should be promoted to validate the preliminary results.