TY - JOUR
T1 - Impaired platelet function reduces myocardial infarct size in Gαq knock-out mice in vivo
AU - Weig, Hans Joerg
AU - Bott-Flügel, Lorenz
AU - Städele, Christian
AU - Winter, Kerstin
AU - Schmidt, Roland
AU - Gawaz, Meinrad
AU - Laugwitz, Karl Ludwig
AU - Seyfarth, Melchior
N1 - Funding Information:
This study was supported by grants from the Technische Universität of Munich (KKF 50-01) and Deutsche Herzstiftung (No F/04/04). We would like to thank especially Diana Grewe who carried out most of the histochemical and cell culture work. We gratefully acknowledge Stefan Offermanns, University Heidelberg, for his generosity in providing the Gα q knock-out strain.
PY - 2008/1
Y1 - 2008/1
N2 - Platelet aggregation and secretion play a crucial role in acute coronary syndromes. In Gαq knock-out mice (Gαq(-/-)) platelet function is eliminated in terms of aggregation and secretion of cytokines. We investigated whether restricted platelet aggregation and secretion reduces myocardial infarct size in vivo. Thirty minute regional myocardial ischemia was followed by 24 h reperfusion (I/R) in vivo. Infarct size was determined by counterstaining. Left ventricular function was measured by ultrasound. Infarct size to area at risk ratio was significantly smaller in Gαq(-/-) mice (5.6 ± 1.6%) compared to wild-type (WT) mice (27.2 ± 3.0%, p < 0.01). Fractional shortening was improved in Gαq(-/-) mice compared to WT (42.2 ± 1.4% versus 30.5 ± 1.4%, respectively, p < 0.01). WT mice, transplanted with Gαq(-/-) bone marrow showed a significant reduction in infarct size compared to control (7.8 ± 2.2% versus 18.4 ± 2.7%, respectively, p < 0.01). Platelets of Gαq(-/-) mice had an impaired aggregation and secretion phenotype. In the in vivo model of ischemia and reperfusion, beyond impaired platelet aggregation, platelet secretion plays an additional role in myocardial infarct extension. Blocking platelet aggregation in combination with secretion might be a promising supplementary therapeutic strategy in acute myocardial infarction.
AB - Platelet aggregation and secretion play a crucial role in acute coronary syndromes. In Gαq knock-out mice (Gαq(-/-)) platelet function is eliminated in terms of aggregation and secretion of cytokines. We investigated whether restricted platelet aggregation and secretion reduces myocardial infarct size in vivo. Thirty minute regional myocardial ischemia was followed by 24 h reperfusion (I/R) in vivo. Infarct size was determined by counterstaining. Left ventricular function was measured by ultrasound. Infarct size to area at risk ratio was significantly smaller in Gαq(-/-) mice (5.6 ± 1.6%) compared to wild-type (WT) mice (27.2 ± 3.0%, p < 0.01). Fractional shortening was improved in Gαq(-/-) mice compared to WT (42.2 ± 1.4% versus 30.5 ± 1.4%, respectively, p < 0.01). WT mice, transplanted with Gαq(-/-) bone marrow showed a significant reduction in infarct size compared to control (7.8 ± 2.2% versus 18.4 ± 2.7%, respectively, p < 0.01). Platelets of Gαq(-/-) mice had an impaired aggregation and secretion phenotype. In the in vivo model of ischemia and reperfusion, beyond impaired platelet aggregation, platelet secretion plays an additional role in myocardial infarct extension. Blocking platelet aggregation in combination with secretion might be a promising supplementary therapeutic strategy in acute myocardial infarction.
KW - Aggregation and secretion
KW - G protein coupled receptor
KW - Gα knock-out
KW - Myocardial infarction
KW - Platelets
UR - http://www.scopus.com/inward/record.url?scp=37549028845&partnerID=8YFLogxK
U2 - 10.1016/j.yjmcc.2007.09.018
DO - 10.1016/j.yjmcc.2007.09.018
M3 - Article
C2 - 18021799
AN - SCOPUS:37549028845
SN - 0022-2828
VL - 44
SP - 143
EP - 150
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 1
ER -