Screening and functional study of key miRNAs in circulating exosomes of hypertension / 中国药理学通报

Aim To clarify the effect of circulating exosomes on hypertension, screen out miRNAs which plays a key role, and explore its function.Methods The plasma exosomes of spontaneously hypertensive rats were extracted and injected into Sprague Dawley rats.The blood pressure changes of rats were detected.Plasma exosomes and exosomal RNA of hypertensive patients and SHR were extracted.Real time PCR was used to verify the expression changes of the selected 8 miRNAs; Western blot was used to detect the expression changes of LKB1 and PTEN protein levels in human umbilical vein endothelial cells transfected with miR-17-5p mimics.Results The plasma exosomes of SHRs significantly increased the blood pressure of SD rats(P<0.05).The expression of miR-17-5p and miR-218-5p in the plasma exosomes of hypertensive patients and SHRs both significantly increased.miR-17-5p inhibitors significantly attenuated the effect of SHR-exos on raising blood pressure.miR-17-5p mimics down-regulated the expression of LKB1 and PTEN in HUVECs cultured in vitro.Conclusions The plasma exosomes of SHR can significantly increase blood pressure of Sprague Dawley rats.miR-17-5p may be the key miRNA.exo-miR-17-5p may promote the occurrence and development of hypertension by regulating the LKB1/PTEN signal.

Hyperglycemia at admission and outcome in elderly patients with acute ST segment elevation myocardial infarction underwent primary percutaneous coronary intervention / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the association between hyperglycemia and outcome in elderly patients with acute ST segment elevation myocardial infarction (STEMI) underwent primary percutaneous coronary intervention (PCI).</p><p><b>METHODS</b>This retrospective analysis was performed on 284 elderly patients (age > or = 60 years) with acute STEMI underwent primary PCI between January 2000 to April 2004 in our department. Patients were divided into 3 groups according to the level of blood glucose on admission: group A, < 7.8 mmol/L; group B, 7.8 - 10.9 mmol/L; group C, > or = 11.0 mmol/L.</p><p><b>RESULTS</b>(1) The proportion of female in group B and group C was greater than that of group A (33.3% vs. 26.5%, P < 0.01; 40.2% vs. 26.5%, P < 0.01). The hospital stay time of group B and group C was significantly longer than that of group A (16.0 days vs. 13.9 days, P < 0.05; 16.6 days vs. 13.9 days, P < 0.05). There were more patients with history of hypertension in group C than that in group A (72.1% vs. 54.9%, P < 0.01). (2) After PCI, the proportion of patients with TIMI myocardial perfusion grade (TMPG) 0-1 in group B and C was greater than that of group A (22.6% vs. 13.3%, P < 0.05; 34.1% vs. 13.3%, P < 0.05). The proportion of patients with TMPG 3 in group B and C was less than that in group A (74.3% vs. 84.4%, P < 0.05; 57.6% vs. 84.4%, P < 0.05). The complication rate of PCI was significantly higher in group C than in group A (42.5% vs. 20.6%, P < 0.01) and group B (42.5% vs. 26.6%, P < 0.01). IABP use was significantly more in group C than that in group A (19.5% vs. 4.9%, P < 0.01) and group B (19.5% vs. 6.4%, P < 0.01). (3) There were more patients with grade of Killip class > or = 2 in group C than that in group A (44.8% vs. 23.5%, P < 0.01) and group B (44.8% vs. 27.7%, P < 0.01). The in-hospital mortality rate (8.0% vs. 1.1%, P < 0.05) and one-year mortality rate (18.7% vs. 3.4%, P < 0.05) of group C were significantly higher than those in group A.</p><p><b>CONCLUSION</b>Hyperglycemia at admission was associated with poor tissue perfusion, cardiac function and prognosis in elderly patients with acute STEMI underwent primary PCI.</p>

Relation of hyperglycemia to ST-segment resolution after primary percutaneous coronary intervention for acute myocardial infarction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hyperglycemia has been shown to be a powerful predictor of poor outcome after ST-segment elevation myocardial infarction (STEMI). This study aimed to evaluate the effect of admission glucose on microvascular flow after successful primary percutaneous coronary intervention (PCI) in patients with STEMI.</p><p><b>METHODS</b>Successful primary PCI was performed in 267 patients with STEMI. The maximum ST elevation of single electrocardiogram (ECG) lead before and 60 minutes after PCI was measured, and patients were then divided into 3 groups according to the degree of ST-segment resolution (STR): absent (<30%), partial (30% to 70%) or complete (> or =70%).</p><p><b>RESULTS</b>Of the 267 patients, 48 (18.0%) had absent STR, 137 (51.3%) experienced partial STR, and 82 (30.7%) had complete STR. The degree of STR decreased with increasing admission glucose levels (P=0.032), and patients with hyperglycemia (serum glucose level > or =11 mmol/L) were more likely to have absent STR (P=0.001). Moreover,hyperglycemia was an independent predictor of incomplete STR (odds ratio, 1.870; 95% confidence interval, 1.038 to 3.371, P=0.037).</p><p><b>CONCLUSIONS</b>Hyperglycemia on admission is associated with abnormal coronary microvascular reperfusion in patients with STEMI after successful primary PCI, which may contribute, at least in part, to the poor outcomes in these patients.</p>

Effects of reperfusion arrhythmia on myocardial apoptosis and left ventricular remodeling in patients with acute myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe plasma soluble Fas/APO-1 concentration in patients with reperfusion arrhythmia immediately after coronary reperfusion in patients with acute myocardial infarction (AMI) and to investigate the impact of reperfusion arrhythmia on left ventricular (LV) remodeling in AMI patients. To observe the relationship between cardiomyocytes apoptosis with reperfusion arrhythmia in patients with acute myocardial infarction (AMI), and investigate the impact of reperfusion arrhythmia on left ventricular (LV) remodeling in patients with AMI.</p><p><b>METHODS</b>One hundred and fifty-six patients with AMI who received reperfusion therapy were selected as subjects. Fifty-eight patients underwent reperfusion arrhythmia within 24 hour after coronary reperfusion treatment (RA group). Ninety-eight patients did not occurred reperfusion arrhythmia (Non-RA group). Strepavidin-biotin ELISA was used to determine the soluble Fas/APO-1 plasma concentration at baseline, 7 day (d) and 2 - 4 week (W). All patients were followed up with scheduled evaluations of LV function and morphology with left ventriculography for 1 year.</p><p><b>RESULTS</b>1. It was later that the coronary reperfusion occurred in patients of RA group than that of Non-RA group, and the left anterior descending was more frequent infarct related artery (60.3%) than of Non-RA group (36.9%, P < 0.05). 2. The Fas/APO-1 levels in patients of RA group higher than those of Non-RA group at baseline [(13.82 +/- 4.36) microg/L vs (8.19 +/- 3.56) microg/L, P < 0.01]. 3. The highest level of Fas/APO-1 was on 7 d after AMI and the plasma levels of Fas/APO-1 in 2 - 4 W were slightly lower than those in 7 d in the two groups [RA group: (10.91 +/- 3.65) microg/L vs (14.26 +/- 4.98) microg/L, P < 0.05; Non-RA group: (4.69 +/- 1.87) microg/L vs (12.19 +/- 3.25) microg/L, P < 0.01]. However, the Fas/APO-1 level of 2 - 4 W in RA group was slightly higher than the level in Non-RA group [(10.91 +/- 3.65) microg/L vs (4.69 +/- 1.87) microg/L, P < 0.01]. 4. There was on difference between two groups in left ventricular ejection fraction (LVEF) and the left ventricular end-diastolic dimension (LVEDD) one week after AMI [LVEF: (47.7 +/- 9.6)% vs (49.2 +/- 8.9)%, P > 0.05; LVEDD: (59.7 +/- 10.3) mm vs (57.4 +/- 12.4) mm, P > 0.05]. 5. In the Non-RA group, the LVEF significantly increased from 1 W phase to the 1-year phase [from (49.2 +/- 8.9)% to (59.5 +/- 9.2)%, P < 0.05], but unchanged in the 58 patients without reperfusion arrhythmia [from (47.7 +/- 9.6)% to (49.9 +/- 10.1)%, P > 0.05]. The LVEF of Non-RA group was slightly higher than that of RA group at 1 year [(59.5 +/- 9.2)% vs (49.9 +/- 10.1)%, P < 0.05]. The LVEDD had no significant difference between two groups, but there was downtrend in the Non-RA group at 1 year after AMI.</p><p><b>CONCLUSION</b>Reperfusion arrhythmia was related with cardiomyocytes apoptosis in patients with AMI, and might influence left ventricular function and promote LV remodeling.</p>

Equivalent cardioprotective effect of "half-conditioning" and post-conditioning in a canine model of myocardial ischemia and reperfusion / 中华心血管病杂志

<p><b>OBJECTIVE</b>To study the effects of "half-conditioning", a modified postconditioning process, on myocardial injury induced by severe myocardial ischemia/reperfusion (I/R) in anesthetized dogs.</p><p><b>METHODS</b>Mongrel dogs of both sexes were subjected to 40 min ischemia (coronary blood flow reduced by 80% via controlled coronary stenosis). At the end of ischemia, dogs were randomly received one of the following treatments: (1) control, reperfusion for 3 h (n = 7); (2) post-conditioning, three cycles of ischemia 30 s followed by reperfusion for 30 s and then reperfusion for 3 h (n = 7); (3) half-conditioning, coronary blood flow recovered to 50% for 2 min, then 80% for 2 min, thereafter 100% for 3 h (n = 7). Electrocardiogram (ECG), arterial blood pressure and left ventricular pressure were monitored throughout the experiment. Plasma creatine kinase (CK) and lactate dehydrogenase (LDH) activity were measured spectrophotometrically. Myocardial necrosis was defined by TTC-staining.</p><p><b>RESULTS</b>Compared with control animals, arrhythmia incidence, LVEDP at 2 and 3 h reperfusion, CK and LDH were significantly reduced in animals received post-conditioning and half-conditioning treatments, infarct size as a percentage (%) of the area at risk was also significantly reduced by post-conditioning and half-conditioning treatments. No differences were observed in the post-conditioning and half-conditioning groups.</p><p><b>CONCLUSION</b>Half-conditioning exerts the same cardioprotective effects on post-ischemic hearts as postconditioning.</p>