Endothelial progenitor cells in the host defense response

Extensive injury of endothelial cells in blood vasculature, especially in the microcirculatory system, frequently oc-curs in hosts suffering from sepsis and the accompanied systemic inflammation. Pathological factors, including toxic components derived from invading microbes, oxidative stress associated with tissue ischemia/ reperfusion, and vessel active mediators generated during the inflammatory response, are known to play impor-tant roles in mediating endothelial injury. Collapse of microcirculation and tissue edema developed from the fail-ure of endothelial barrier function in vital organ systems, including the lung, brain, and kidney, are detrimental, which often predict fatal outcomes. The host body possesses a substantial capacity for maintaining vascular ho-meostasis and repairing endothelial damage. Bone marrow and vascular wall niches house endothelial progeni-tor cells (EPCs). In response to septic challenges, EPCs in their niche environment are rapidly activated for proliferation and angiogenic differentiation. In the meantime, release of EPCs from their niches into the blood stream and homing of these vascular precursors to tissue sites of injury are markedly increased. The recruited EPCs actively participate in host defense against endothelial injury and repair of damage in blood vasculature via direct differentiation into endothelial cells for re-endothelialization as well as production of vessel active me-diators to exert paracrine and autocrine effects on angiogenesis/vasculogenesis. In recent years, investigations on significance of EPCs in host defense and molecular signaling mechanisms underlying regulation of the EPC response have achieved substantial progress, which promotes exploration of vascular precursor cell-based approaches for effective prevention and treatment of sepsis-induced vascular injury as well as vital organ system failure.(c) 2022 Elsevier Inc. All rights reserved.

Automated summary

Extensive injury of endothelial cells in sepsis and systemic inflammation is caused by pathological factors such as microbial toxins, oxidative stress, and inflammatory mediators. The failure of endothelial barrier function leads to microcirculatory collapse and tissue edema, which can be fatal. The activation of endothelial progenitor cells (EPCs) in response to septic challenges and their recruitment to injured tissues contribute to endothelial repair and angiogenesis. Understanding the molecular signaling mechanisms underlying the EPC response offers potential approaches for preventing and treating sepsis-induced vascular injury and organ failure.