SUMO1 Deficiency Exacerbates Neurological and Cardiac Dysfunction after Intracerebral Hemorrhage in Aged Mice

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Transl Stroke Res


Small ubiquitin-like modifier 1 (SUMO1) reduces cardiac hypertrophy and induces neuroprotective effects. Previous studies have found that intracerebral hemorrhage (ICH) provokes cardiac deficit in the absence of primary cardiac diseases in mice. In this study, we tested the hypothesis that SUMO1 deficiency leads to worse brain and heart dysfunction after ICH and SUMO1 plays a key role in regulating brain-heart interaction after ICH in aged mice. Aged (18-20 months) female SUMO1 null (SUMO1(-/-)) mice and wild-type (WT) C57BL/6 J mice were randomly divided into four groups (n = 8/group): (1) WT-sham group, (2) SUMO1(-/-)-sham group, (3) WT-ICH group, and (4) SUMO1(-/-)-ICH group. Cardiac function was measured by echocardiography. Neurological and cognitive functional tests were performed. Mice were sacrificed at 10 days after ICH for histological and immunohistochemically staining. Compared with WT-sham mice, WT-ICH mice exhibited (1) significantly (P < 0.05) decreased SUMO1 expression in heart tissue, (2) evident neurological and cognitive dysfunction as well as brain white matter deficits, (3) significantly increased cardiac dysfunction, and (4) inflammatory factor expression in the heart and brain. Compared with WT-ICH mice, SUMO1(-/-)-ICH mice exhibited significantly increased: (1) brain hemorrhage volume, worse neurological and cognitive deficits, and increased white matter deficits; (2) cardiac dysfunction and cardiac fibrosis; (3) inflammatory response both in heart and brain tissue. Aged SUMO1-deficient female mice subjected to ICH not only exhibit increased neurological and cognitive functional deficit but also significantly increased cardiac dysfunction and inflammatory cell infiltration into the heart and brain. These data suggest that SUMO1 plays an important role in brain-heart interaction.

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ePub ahead of print