Einfluss des Gαq-Proteins auf die myokardiale Infarktgröße der knochenmarktransplantierten Gαq-Knockout-Maus im Ischämie/Reperfusionsmodell
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vor 18 Jahren
Influence of the Gαq-protein on myocardial infarct size of the bone
marrow-engrafted Gαq-knockout-mouse in a ischemia/reperfusion-model
Platelets play a key role in the pathogenesis of an acute
myocardial infarction. Thrombus formation, which is mediated by the
activation of platelets, results in the occlusion of the coronary
artery. On the other hand, agglutinated platelets in the small
myocardial vessels impair the myocardial microcirculation. Due to
their pro-inflammatory effects, platelets also contribute to the
pathogenesis of ischemia/reperfusion injury. The myocardium of
Gαq-deficient mice showed a reduced susceptibility to ischemia and
reperfusion compared to that of wild-type mice (HEUER, in
preparation). Activation of platelets lacking the Gαq-protein is
markedly impaired, resulting not only in an increased haemophilia
but also in a decreased thrombophilia of Gαq-deficient mice. A bone
marrow transplantation was performed to investigate whether the
impaired platelet-activation is responsible for the reduced
susceptibility of Gαq-deficient mice to ischemia/reperfusion
injury. Wild-type mice were lethally irradiated to facilitate the
engraftment of bone marrow cells of Gαq-deficient mice and vice
versa. A reconstitution phase of at least 90 days for both groups
guaranteed, that blood of wild-type mice contained normal levels of
Gαq-deleted platelets, while blood of Gαq- deficient mice contained
only wild-type platelets. Afterwards, according to the study of
HEUER (in preparation), myocardial ischemia was artificially
induced by surgically ligating the left coronary artery for 30
minutes and was followed by a reperfusion phase of 24 hours. Heart
function of both groups was examined by echocardiography before and
after surgery. After euthanasia the size of infarction-area to area
at risk (I/AAR) and infarction-area to left ventricle (I/LV) in the
stained hearts was determined by planimetry. As a result neither
the cardioechography (relative difference of fractional shortening
prae and post op: 17, 1 % ± 2,9 % (SEM) versus 10,8 % ± 4,0 %
(SEM)) nor the infarct-sizes (I/AAR: 18,2 % ± 4,2 % (SEM) versus
10,0 % ± 3,7 % (SEM); I/LV: 9,5 % ± 2,7 % (SEM) versus 5,6 % ± 2,2
% (SEM)) showed any significant differences between the two groups.
In conclusion it could be assumed, that the impaired
platelet-activation is not the only reason for the different
susceptibility of wild-type and Gαq-deficient mice to
ischemia/reperfusion injury; in fact, the reduced susceptibility of
Gαq-deficient mice seems to be a result of both - their impaired
platelet-activation and unknown protecting effects based on the
absence of the Gαq-protein in other cells such as cardiomyocytes.
marrow-engrafted Gαq-knockout-mouse in a ischemia/reperfusion-model
Platelets play a key role in the pathogenesis of an acute
myocardial infarction. Thrombus formation, which is mediated by the
activation of platelets, results in the occlusion of the coronary
artery. On the other hand, agglutinated platelets in the small
myocardial vessels impair the myocardial microcirculation. Due to
their pro-inflammatory effects, platelets also contribute to the
pathogenesis of ischemia/reperfusion injury. The myocardium of
Gαq-deficient mice showed a reduced susceptibility to ischemia and
reperfusion compared to that of wild-type mice (HEUER, in
preparation). Activation of platelets lacking the Gαq-protein is
markedly impaired, resulting not only in an increased haemophilia
but also in a decreased thrombophilia of Gαq-deficient mice. A bone
marrow transplantation was performed to investigate whether the
impaired platelet-activation is responsible for the reduced
susceptibility of Gαq-deficient mice to ischemia/reperfusion
injury. Wild-type mice were lethally irradiated to facilitate the
engraftment of bone marrow cells of Gαq-deficient mice and vice
versa. A reconstitution phase of at least 90 days for both groups
guaranteed, that blood of wild-type mice contained normal levels of
Gαq-deleted platelets, while blood of Gαq- deficient mice contained
only wild-type platelets. Afterwards, according to the study of
HEUER (in preparation), myocardial ischemia was artificially
induced by surgically ligating the left coronary artery for 30
minutes and was followed by a reperfusion phase of 24 hours. Heart
function of both groups was examined by echocardiography before and
after surgery. After euthanasia the size of infarction-area to area
at risk (I/AAR) and infarction-area to left ventricle (I/LV) in the
stained hearts was determined by planimetry. As a result neither
the cardioechography (relative difference of fractional shortening
prae and post op: 17, 1 % ± 2,9 % (SEM) versus 10,8 % ± 4,0 %
(SEM)) nor the infarct-sizes (I/AAR: 18,2 % ± 4,2 % (SEM) versus
10,0 % ± 3,7 % (SEM); I/LV: 9,5 % ± 2,7 % (SEM) versus 5,6 % ± 2,2
% (SEM)) showed any significant differences between the two groups.
In conclusion it could be assumed, that the impaired
platelet-activation is not the only reason for the different
susceptibility of wild-type and Gαq-deficient mice to
ischemia/reperfusion injury; in fact, the reduced susceptibility of
Gαq-deficient mice seems to be a result of both - their impaired
platelet-activation and unknown protecting effects based on the
absence of the Gαq-protein in other cells such as cardiomyocytes.
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