Abstract 15921: Autoimmunity against Cardiac Troponin I in Ischemia/Reperfusion Injury
Objectives: General opinion agrees on the concept that early reperfusion of the ischemic myocardium improves outcome by limiting infarct expansion and promoting tissue repair. But on the other hand, the reestablishment of coronary blood flow can, paradoxically, also precipitate myocardial damage through reperfusion injury. Autoantibodies against cardiac troponin I (cTnI) have been associated with deleterious effects on the myocardium, as previously demonstrated in various murine experimental models. In the present study, we investigated the impact of autoimmunity against cTnI in reperfusion injury, which represents a possible drawback of established reperfusion strategies.
Methods: Two groups of A/J mice were immunized either with murine cTnI (n = 13) or a control buffer (n = 17). 21 days later, mice were subjected to myocardial ischemia/reperfusion injury. After 90 days, cardiac function was assessed by echocardiography and blood samples were collected prior to euthanization. Hearts were obtained for further histopathologic evaluation and splenocytes were isolated to profile the pattern of activated cytokines specific to cTnI.
Results: Mice subjected to cTnI pre-immunization before reperfusion injury exhibited a higher cTnI-autoantibody titer along with a markedly decreased fractional shortening (mean FS 31.5 ± 5.8 % vs. 37.8 ± 1.1 %, p < 0.01) and increased inflammation and fibrosis scores on histological examination in contrast to the control group. In accordance with these findings, the cytokine expression pattern (increased IL-2 and IFN-γ production by splenocytes from mice undergoing cTnI-immunization and ischemia/reperfusion injury) showed a Th1-mediated inflammatory response. In contrast, the Th2 subset (decreased IL-6 and IL-10) and the cytokines (TNF-α, IL-1β) related to monocyte/macrophage activity were downregulated.
Conclusions: Our results demonstrate that a pre-exposition to cTnI sufficient to mediate an autoimmune response against cTnI leads to an enhanced reperfusion injury. Transferred to clinical practice, the present study suggests that patients undergoing recurrent revascularizations inducing an autoimmune response against cTnI may be at increased risk for enhanced myocardial damage.
- © 2010 by American Heart Association, Inc.