Premium
Cx40‐deficient mice reveal angiotensin II‐dependent and –independent mechanisms of post‐ischemic injury in a model of peripheral artery disease
Author(s) -
Fang Jennifer SheaYing,
Angelov Stoyan N,
Good Miranda E,
Simon Alexander M,
Burt Janis M
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1092.16
Subject(s) - losartan , angiotensin ii , medicine , inflammation , angiotensin ii receptor type 1 , ischemia , peripheral , vasodilation , cardiology , receptor , endocrinology
The role of vascular connexins (Cx), component proteins of gap junctions, remains unclear. Cx40 knockout (Cx40 −/− ) mice have reduced endothelial coupling and increased angiotensin II (AngII) signaling. In this study, our objective was to dissect the mechanisms that might regulate post‐ischemic tissue injury in a surgical model of peripheral artery disease. We report that Cx40 −/− mice suffer post‐ischemic distal necrosis and reduced limb flow. Short‐term pre‐treatment with losartan, an AngII receptor antagonist, did not alter post‐ischemic outcome, whereas long‐term losartan improved surgical limb flow, reduced macrophage infiltration, and delayed – but did not prevent – post‐ischemic necrosis. These findings indicate that prolonged AT1R signaling is partially involved in post‐ischemic tissue damage, and may regulate inflammation and upstream collateral remodeling. However, our observations also demonstrate that AT1R‐independent mechanisms also participate in tissue injury in Cx40 −/− animals, and may involve loss of Cx40‐mediated conduction of vasodilatory or anti‐inflammatory signals. Support: AHA550158Z (JMB), HL064232 (AMS), AHA0715532Z (JSF), AHA09PRE2060122 (JSF).