Abstract WMP82: Brain-Derived Microparticles Mediate Cardiac Dysfunction After Stroke

Background and Purpose: Brain injury may induce cardiac damage. Microparticles (MPs, size between 0.1-1mm) are involved in intercellular communication and regulate thrombosis and inflammation. In this study, we investigate whether Brain-derived MPs (BDMP) after stroke contribute to stroke induced heart dysfunction. Method: 1) Human study: Serum GFAP+MP levels measured by Flow cytometry were obtained from acute stroke patients (≤ 3d post stroke) and normal subjects (n=15/group). 2) Animal study: Adult (8-9m) male C57BL/6J mice were subjected to distal middle cerebral artery occlusion (dMCAo) or sham control. BDMP were extracted from ischemic brain 24h after dMCAo by ultracentrifugation. BDMP (1.5х10 8 ) were injected (iv) into normal 8-9 m old C57BL/6J mice daily for 3 consecutive days (n=10). PBS was injected as control (n=9). Using Echocardiography, cardiac function was measured 3 and 30 days after injection. 3) In vitro study: Cultured primary cardiomyocytes were treated with: A) control; B-C) BDMP derived from sham or dMCAo mice; D-E) serum-MP derived from sham or dMCAo mice. Immunostaining, PCR, Western blot and LDH measurements were employed. Result: 1) Human study: Stroke patients exhibited significant increase of GFAP+MP levels in serum compared to normal subjects. 2) Animal-study: Compared with PBS control group, injection of BDMP results in a significant (p<0.01): A) decrease in cardiac function identified by decreasing LVEF (left ventricular ejection fraction), LVSF (LV systolic fraction) at 3 and 30d post injection; B) increases cardiac fibrosis identified by Sirius Red Staining and increases of cardiac thrombosis measured by CD41, as well as increases leukocyte infiltration in the heart. 3) In vitro study: BDMP and serum-MP derived from dMCAo mice significantly induce cardiomyocyte death, and cardiomyocyte inflammatory factors (MCP1, VCAM1, ICAM, TNFα and TLR2) gene expression compared to sham BDMP or sham serum-MP, respectively; BDMP induces significantly increased cardiomyocyte death, and cardiomyocyte inflammatory factor compared with serum-MP. Conclusion: BDMP mediate cardiac dysfunction after stroke. BDMP induced cardiac dysfunction may be associated with increased inflammatory response and thrombosis in the heart.