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Reperfusion of chronic tissue ischemia: nitrite and dipyridamole regulation of innate immune responses
Author(s) -
Pattillo Christopher B.,
Fang Kai,
Terracciano Justin,
Kevil Christopher G.
Publication year - 2010
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2010.05737.x
Subject(s) - dipyridamole , ischemia , arteriogenesis , nitric oxide , medicine , angiogenesis , pharmacology , innate immune system , immune system , immunology , cardiology
Chronic and intermittent ischemic vascular disorders represent a burgeoning clinical challenge. Previous studies have focused on the idea that therapeutic angiogenesis strategies could alleviate tissue ischemia; however, it is now appreciated that vascular disease is not simply limited to vascular wall cells but also influenced by simultaneously occurring inflammatory responses. Our laboratory has discovered that pharmacological treatment of permanent tissue ischemia with dipyridamole significantly augments ischemic tissue reperfusion, angiogenesis, and arteriogenesis over time. We have found that the beneficial effects of dipyridamole therapy are due to its ability to increase tissue nitric oxide bioavailability that corrects tissue redox imbalance. Importantly, we have also discovered that dipyridamole treatment invoking nitric oxide (NO) production significantly downregulates various innate immune response genes during chronic ischemic tissue injury. These findings demonstrate that dipyridamole‐induced production of nitrite/NO significantly decreases inflammatory responses while increasing vascular growth in ischemic tissues.