Mechanisms of I/R-Induced Endothelium-Dependent Vasodilator Dysfunction

Advances in Pharmacology
Ronald J Korthuis

Abstract

Ischemia/reperfusion (I/R) induces leukocyte/endothelial cell adhesive interactions (LECA) in postcapillary venules and impaired endothelium-dependent, NO-mediated dilatory responses (EDD) in upstream arterioles. A large body of evidence has implicated reactive oxygen species, adherent leukocytes, and proteases in postischemic EDD dysfunction in conduit arteries. However, arterioles represent the major site for the regulation of vascular resistance but have received less attention with regard to the mechanisms underlying their reduced responsiveness to EDD stimuli in I/R. Even though leukocytes do not roll along, adhere to, or emigrate across arteriolar endothelium in postischemic intestine, recent work indicates that I/R-induced venular LECA is causally linked to EDD in arterioles. An emerging body of evidence suggests that I/R-induced EDD in arterioles occurs by a mechanism that is triggered by LECA in postcapillary venules and involves the formation of signals in the interstitium elicited by the proteolytic activity of emigrated leukocytes. This activity releases matricryptins from or exposes matricryptic sites in the extracellular matrix that interact with the integrin αvβ3 to induce mast cell chymase-dependent formation of...Continue Reading

Citations

Jul 25, 2019·International Journal of Molecular Sciences·Kuo-Hua LeeDer-Cherng Tarng
Mar 9, 2019·Free Radical Biology & Medicine·Hong YuRonald J Korthuis

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