ABSTRACT
OBJECTIVE@#To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis.@*METHODS@#A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities.@*RESULTS@#DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01).@*CONCLUSION@#DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.
Subject(s)
Mice , Animals , Tumor Suppressor Protein p53/metabolism , Endothelial Cells/metabolism , Exosomes/metabolism , bcl-2-Associated X Protein/metabolism , Myocardium/metabolism , Myocardial Infarction/drug therapy , Apoptosis , MicroRNAs/metabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of Chinese herbal medicine for benefiting qi and nourishing yin to promote the blood circulation (abbr. as CHM) in promoting ventricular wall motion and myocardial contraction in acute myocardial infarction (AMI) patients after revascularization.</p><p><b>METHODS</b>Subjects were 80 AMI patients after revascularization, of those, the 40 patients in the TCM group were treated with Xinyue Capsule and compound Tanshinon Tablet upon the basic conventional Western medical treatment and the other 40 in the control group were given conventional Western medicine alone, the course for them all was 3 months. Cardiac function indexes, including left ventricular ejection fraction (LVEF), wall motion indices, normal myocardial percentage (NMP), longitudinal systolic peak strain (LSPS) and rate (LSPSR), were observed by Doppler ultrasound under dobutamine stress at the 14 days after revascularization and the end of 3-month treatment.</p><p><b>RESULTS</b>Except the 5 cases (3 in the TCM group and 2 in the control group) dropped out in the observation period, the trial was completed in 75 patients totally. LVEF, NMP, minus LSPS of left ventricular anterior apex and inferior basement, minus LSPSR of anterior apex, middle, basement, and minus LSPSR of inferior middle, basement were more significantly increased in Chinese medicinal treatment group than those in the control group at 14-day after revascularization (P < 0.01). The treatment group, minus LSPS and minus LSPSR of the left ventricular anterior apex and the inferior basement were at markedly higher levels compared with the controls at 3-month after revascularization (P < 0.05). Minus LSPSR of the left ventricular anterior apex and the inferior basement in the treatment group at 3-month was higher than that at 14-day after revascularization (P < 0.05).</p><p><b>CONCLUSION</b>CHM combining with conventional Western medicine treatment could improve the left ventricular contractive function and wall motion in AMI patients after revascularization.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Angioplasty, Balloon, Coronary , Combined Modality Therapy , Drugs, Chinese Herbal , Therapeutic Uses , Heart Ventricles , Myocardial Contraction , Myocardial Infarction , Therapeutics , Phytotherapy , Qi , Stroke Volume , Yin-YangABSTRACT
<p><b>OBJECTIVE</b>To observe the effects of Chinese drugs for supplementing qi, nourishing yin and activating blood circulation on the myocardial perfusion in acute myocardial infarction (AMI) patients after revascularization.</p><p><b>METHODS</b>Eighty patients with anterior or inferior ventricular wall AMI, who had received revascularization by intravenous thrombolysis or coronary bypass, were randomized into the treated group and the control group equally, both treated with conventional Western medical treatment, but combined, respectively, with Xinyue Capsule (, XYC) plus Composite Salvia Tablet (CST) and placebo for 3 months. Dobutamine stress echocardiography (DSE) was performed 14 days and 3 months after revascularization, respectively on every patient to observe blood perfusion extent (b value), myocardial perfusion velocity (k value) and local blood fl ow volume (k x b) in left ventricular infarction-related vascular segments under stressed state.</p><p><b>RESULTS</b>With 5 cases dropping out in the observation period (3 in the treated group and 2 in the control group), the trial was completed in 75 patients in total. The 14-day DSE shows that the b value and k x b value of left anterior ventricular wall mid segment and apex segment, and the k value of apex segment in patients with anterior wall AMI, as well as the b value and k x b of basal segment in patients with inferior wall AMI in the treated group were significantly higher than those in the control group (P<0.05 or P<0.01). The 3-month DSE shows that the b value of apex segment, k x b value of basal segment, mid segment and apex segment of left anterior ventricular wall in patients with anterior wall AMI as well as the b value and k x b value of basal segment of left inferior ventricular wall in patients with inferior wall AMI were all higher in the treated group than those in the control group, respectively (P<0.05). The comparison between 14-day DSE and 3-month DSE in the treated group showed that the b value of apex segment of left anterior ventricular wall in patients with anterior wall AMI and the k x b value of apex segment and mid segment of left inferior ventricular wall in patients with inferior wall AMI significantly increased along with the on-going treatment (P<0.05).</p><p><b>CONCLUSION</b>Therapy with Chinese drugs for supplementing qi, nourishing yin and activating blood circulation in combination with conventional Western medical treatment could obviously improve the blood perfusion at the myocardial tissue level in infarction-related vascular segments.</p>