Procalcitonin Impairs Endothelial Cell Function and Viability

Abstract

This study found that procalcitonin itself impaired several aspects of endothelial cell function. Procalcitonin-induced loss of endothelial barrier function may contribute to capillary leakage and therapy-refractory hypotension during sepsis. Anti-angiogenic properties of procalcitonin at low concentrations could also identify procalcitonin as a mediator of vascular disease associated with the metabolic syndrome. Future studies are needed to further test procalcitonin as a potential therapeutic target for preserving vascular dysfunction during acute and chronic inflammatory disorders.

Overview of procalcitonin in pregnancy and in pre-eclampsia

“…The increase of circulating proinflammatory cytokines in PE can be responsible for the augmentation of systemic PCT levels; furthermore, as we have previously discussed, increased PCT levels induce proinflammatory cytokine production that stimulates PCT release which, in turn, triggers the production of PCT itself, causing a positive loop of PCT secretion [5]. Another role that PCT could play in PE pathogenesis is connected with its cytotoxic activity on hepatocytes and endothelium [39,40]. Indeed, it is well known that peculiar characteristics of PE are endothelial dysfunction and liver damage [70].…”

“…PCT with TNF-α induces endothelial barrier disruption and (at concentrations of 0·02 ng/ml) reduces endothelial cell migration and in-vitro tube formation. The mechanisms are unclear and need further investigation [39].…”

“…PCT impair the function and viability of human hepatocytes and endothelium and exert general cytotoxicity in vitro [39,40]. PCT with TNF-α induces endothelial barrier disruption and (at concentrations of 0·02 ng/ml) reduces endothelial cell migration and in-vitro tube formation.…”

Endothelial cells and organ function: applications and implications of understanding unique and reciprocal remodelling

“…Endothelial activation in response to disturbed flow underlies atherosclerosis, a condition also shown to result from damage to the endothelial glycocalyx , but also results in a feed‐forward loop that exacerbates the condition and fosters the establishment of further and wide‐ranging complications. The same is observed in metabolic syndrome and the inability to coordinate a response to local vasodilating factors with the need to limit nutrient absorption and transport to an already overwhelmed tissue .…”

“…Secondary to the primary cause of the malaise, the microvascular reactions to pathological challenges often result in either severe comorbidity, such as in the case of respiratory disease ( e.g. COPD and acute respiratory distress syndrome) or sepsis , where EC activation compounds primary symptoms through added oedema, permeability and positive feedback of inflammatory signals. Endothelial activation in response to disturbed flow underlies atherosclerosis, a condition also shown to result from damage to the endothelial glycocalyx , but also results in a feed‐forward loop that exacerbates the condition and fosters the establishment of further and wide‐ranging complications.…”