The complement—dendritic cell–endothelial cell crosstalk in vascular inflammation

Inflammation is a highly coordinated process involving multiple immune components, including the complement system, dendritic cells (DCs), and endothelial cells (ECs). All of them play pivotal roles in immunity and host defense and have a significant impact on cardiovascular health and disease. While individual functions of the complement system, DCs and ECs are well-characterised, their multifaceted interplay in modulating inflammation and disease is insufficiently elucidated. The complement system exerts predominantly pro-inflammatory effects, influencing the immune, the cardiovascular, and the nervous systems. DCs bridge innate and adaptive immunity, shaping T-cell and B-cell responses depending on their maturation state. At the interface between tissues and circulation, ECs regulate immune cell trafficking and vascular homeostasis, while endothelial dysfunction or injury contributes to cardiovascular disorders such as atherosclerosis, hypertension, heart failure, or acute thrombotic events. We have to understand the dynamic crosstalk between the complement system, DCs and ECs, which are important for cardiovascular systems biology, to be able to identify new research avenues and potential therapeutic strategies. This article reviews current insights into these molecular networks discussing their impact on inflammation and cardiovascular pathology. By elucidating these mechanisms, innovative apporaches to prevent and manage cardiovascular diseases may emerge.