4.7 Review

Vascular endotheliitis associated with infections: Its pathogenetic role and therapeutic implication

Journal

BIOCHEMICAL PHARMACOLOGY
Volume 197, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2022.114909

Keywords

COVID-19; Endothelial cells; Endotheliitis; Organ dysfunction; Sepsis

Funding

  1. Japan Society for Promotion of Science [17K08586, 19H03757, 20K17776]

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Vascular endotheliitis plays a crucial role in immune responses, inflammation, and infectious pathologies. It is strongly associated with the pathogenesis of diseases such as COVID-19 and sepsis. Protecting endothelial cells and reversing vascular endotheliitis can be the main therapeutic goal for these diseases.
Vascular endothelial cells are major participants in and regulators of immune responses and inflammation. Vascular endotheliitis is regarded as a host immune-inflammatory response of the endothelium forming the inner surface of blood vessels in association with a direct consequence of infectious pathogen invasion. Vascular endotheliitis and consequent endothelial dysfunction can be a principle determinant of microvascular failure, which would favor impaired perfusion, tissue hypoxia, and subsequent organ failure. Emerging evidence suggests the role of vascular endotheliitis in the pathogenesis of coronavirus disease 2019 (COVID-19) and its related complications. Thus, once initiated, vascular endotheliitis and resultant cytokine storm cause systemic hyperinflammation and a thrombotic phenomenon in COVID-19, leading to acute respiratory distress syndrome and widespread organ damage. Vascular endotheliitis also appears to be a contributory factor to vasculopathy and coagulopathy in sepsis that is defined as life-threatening organ dysfunction due to a dysregulated response of the host to infection. Therefore, protecting endothelial cells and reversing vascular endotheliitis may be a leading therapeutic goal for these diseases associated with vascular endotheliitis. In this review, we outline the etiological and pathogenic importance of vascular endotheliitis in infection-related inflammatory diseases, including COVID-19, and possible mechanisms leading to vascular endotheliitis. We also discuss pharmacological agents which may be now considered as potential endotheliitis-based treatment modalities for those diseases.

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