crt-0066101 and Myocardial-Infarction

The aim of this study is to investigate the role of platelets in anxiety in myocardial infarction (MI).. A protein kinase D (PKD) inhibitor CRT0066101 was administrated to MI rat models. Open-field (OF) test, dark-light transfer (DLT) test and elevated plus maze (EPM) test were used to assess anxiety of animals. Platelets granule releasing was evaluated by ATP releasing assay and flow cytometry detecting CD62P. ELISA was used to measure the levels of vWF, soluble tissue factor (sTF) and IGF1 in serum. Protein phosphorylations were evaluated with western blotting. 171 patients with MI, 189 patients with stable CAD (SCAD) and 200 healthy volunteers (HV) were included in the population study. HAM-A was used to evaluate the anxiety.. In the animal study, PKD inhibitor significantly suppressed platelets granule releasing and serum IGF1 levels (P < 0.05) in MI rats without affecting serum levels of vWF and sTF. MI rats exhibited significantly promoted anxiety-like behaviors (P < 0.05) which was attenuated by PKD inhibitor administration (P < 0.05). In the cross-sectional population study, aggravated anxiety, endothelial damage and platelets granule releasing were found in MI patients. Serum vWF (r = 0.790, P < 0.001) and sTF (r = 0.510, P < 0.001) were significantly correlated with platelets granule releasing. Platelets granule releasing was correlated with serum IGF1 level (r = 0.872, P < 0.001). Anxiety was significantly and positively correlated with platelet granule releasing (r = 0.752, P < 0.001), serum vWF (r = 0.790, P < 0.001), serum sTF (r = 0.510, P < 0.001) and serum IGF1 (r = 0.774, P < 0.001) levels. Multivariate analysis identified platelet activation (OR = 1.58, 95% CI 1.07-2.32, P = 0.022) and IGF1 serum level (OR = 1.05 95% CI 1.04-1.06, P < 0.001) were significantly and positively correlated with anxiety in MI patients after adjustments.. Anxiety is exacerbated in MI via endothelial damage-induced platelets granule releasing-mediated IGF1.

Topics: Animals; Anxiety; Behavior, Animal; Blood Platelets; Case-Control Studies; Coronary Artery Disease; Cross-Sectional Studies; Endothelium, Vascular; Female; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Myocardial Infarction; Protein Kinase C; Protein Kinase C-alpha; Pyrimidines; Rats, Sprague-Dawley