Abstract WMP77: SUMO1 Plays an Important Role in Cardiac Dysfunction After Intracerebral Hemorrhage in Aged Mice

Abstract

Background: The conjugation of the small ubiquitin-like modifier1 (SUMO1) plays an important role in numerous biological processes, including DNA repair and signal transduction. SUMO1 also reduces cardiac oxidative stress and hypertrophy as well as induces neuroprotective effects. Intracerebral hemorrhage (ICH) induces cardiac deficit in the absence of primary cardiac diseases in young adult wild type mice. In this study, we tested the hypothesis that SUMO1 plays a key role in regulating brain-heart interaction after ICH, and SUMO1 deficit leads to worse brain and heart deficit after ICH in aged mice. Methods: Aged (16-20 months) female Sumo1-deficient (SUMO1-/-) mice or wild-type (SUMO1+/+) mice were subjected to ICH by injecting collagenase IV into the basal ganglia. Cardiac function was measured by echocardiography before ICH induction and at 7 days after ICH. Modified neurological severity (mNSS) ,foot-fault and adhesive removal tests were performed at 1, 3, 6 days after ICH to investigate neurological function. Cognitive functional tests (odor and novel objective tests) were performed before sacrificing the mice at 10 days after ICH, and then histological and immunohistochemically staining were used to evaluate the mechanisms. Results: Compared to SUMO1+/+ mice, SUMO1-/- mice did not exhibit significant cardiac deficit before ICH in aged mice. Compared to SUMO1+/+ICH mice, SUMO1-/-ICH mice exhibit significantly (p<0.05) increased: 1) brain hemorrhage volume and induced worse neurological and cognitive deficits, 2) cardiac dysfunction identified by decreased cardiac contractile function measured by left ventricular ejection fraction (LVEF) and fractional shortening (FS); 3) cardiac hypertrophy and fibrosis; 4) ionized calcium binding adaptor molecule (IBA1) positive macrophages/microglia and CD45 positive leukocyte infiltration into both heart and brain tissue. Conclusions: Aged SUMO1 deficient mice subjected to ICH not only exhibit increased neurological and cognitive functional deficit, but also significantly increased cardiac dysfunction and inflammatory cell infiltration into heart. These data suggest that SUMO1 plays an important role in brain-heart interaction and SUMO1 impacts brain-cardiac dysfunction after ICH.