Baoxin Liu

The Protective Effect of Lacidipine on Myocardial Remodeling Is Mediated by the Suppression in Expression of GPR78 and CHOP in Rats

Lacidipine (LAC) is now widely used for the treatment of hypertension and further can prevent cardiac hypertrophy and remodeling. However, the underlying mechanism has not been fully understood. In this study, we examined the protective effects of LAC on cardiac remodeling in spontaneously hypertensive rats (SHR) and investigated the possible mechanism. Four weeks after administration of the designated drugs, blood pressure, left ventricular mass index (LVMI), and rterial pressure (MAP) were measured. The endoplasmic reticulum stress (ERS) parameters such as GRP78 and CHOP expressions in cardiomyocytes were also detected by immunohistochemistry. Results showed that the MAP in 0.36 and 0.72u2009mg/kg LAC groups was markedly lowered compared with that of the SHR control group (P < 0.01 or P < 0.05). Moreover, 0.72u2009mg/kg LAC could also significantly decrease the LVMI (P < 0.05). Simultaneously, the results of immunohistochemistry demonstrated that the expression of GRP78 and CHOP was significantly decreased by 0.72u2009mg/kg LAC (P < 0.05), respectively. Our present study suggested that LAC could lower blood pressure and could prevent left ventricular hypertrophy accompanied by inhibiting expression of GRP78 and CHOP in ERS.

Low protein Z plasma level is a risk factor for acute myocardial infarction in coronary atherosclerosis disease patients

OBJECTIVESnTo examine plasma protein Z (PZ) levels in acute myocardial infarction (AMI) and chronic coronary atherosclerosis disease (CCAD) patients without history of AMI and explore its potential clinical significance.nnnMETHODSnPlasma PZ concentrations were measured in 90 AMI patients (Group A), 87 CCAD patients without AMI history who remained free of major clinical events at least one year (Group B), and 88 clinically healthy controls (Group C).nnnRESULTSnPZ was found to be significantly lower (P<0.001) in Group A (1508.5±486.2ng/mL) compared with Group B (1823.0±607.8ng/mL) and C (2001.7±733.0ng/mL) and in Group A+B compared with Group C (Group A+B 1663.1±570.0 ng/mL, P<0.001). No statistically significant difference was reached between Group B and C (P=0.081). PZ level was significantly correlated with concentration of creatine kinase MB, high sensitive-cardiac troponin T, high sensitive C reactive protein, D-dimer and coagulation factor II and may be a useful predictor for AMI (OR: 1.38, 95% CI: 1.13-1.77, P=0.03). Subgroup analysis showed PZ concentration below the lowest tertile (<1398ng/mL) had a significantly increased risk for AMI and CCAD (OR: 3.39; 95% CI: 1.12-10.31; P=0.03 and OR: 7.39; 95% CI: 2.62-20.79; P<0.001 respectively).nnnCONCLUSIONSnPZ deficiency is found in AMI patients and could potentially reflect the myocardium injury, local coagulation activation and inflammation response during the acute phase of coronary atherosclerosis disease.

The role of mAKAPβ in the process of cardiomyocyte hypertrophy induced by angiotensin II

Angiotensin II (AngII) is the central product of the renin-angiotensin system (RAS) and this octapeptide contributes to the pathophysiology of cardiac hypertrophy and remodeling. mAKAPβ is an A-kinase anchoring protein (AKAP) that has the function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. In this study, we aimed to investigate the role of mAKAPβ in AngII-induced cardiomyocyte hypertrophy and the possible mechanisms involved. Cultured cardiomyocytes from neonatal rats were treated with AngII. Subsequently, the morphology of the cardiomyocytes was observed and the expression of mAKAPβ and cardiomyocyte hypertrophic markers was measured. mAKAPβ-shRNA was constructed for RNA interference; the expression of mAKAPβ and hypertrophic markers, the cell surface area and the [3H]Leucine incorporation rate in the AngII-treated rat cardiomyocytes were detected following RNA interference. Simultaneously, changes in the expression levels of phosphorylated extracellular signal-regulated kinase (p-ERK)2 in the cardiomyocytes were assessed. The cell size of the AngII-treated cardiaomyocytes was significantly larger than that of the untreated cardiomyocytes. The expression of hypertrophic markers and p-ERK2, the cell surface area and the [3H]Leucine incorporation rate were all significantly increased in the AngII-treated cells. However, the expression of mAKAPβ remained unaltered in this process. RNA interference simultaneously inhibited the protein expression of mAKAPβ and p-ERK2, and the hypertrophy of the cardiomyocytes induced by AngII was attenuated. These results demonstrate that AngII induces hypertrophy in cardiomyocytes, and mAKAPβ is possibly involved in this process. The effects of mAKAPβ on AngII-induced cardiomyocyte hypertrophy may be associated with p-ERK2 expression.

Increased risk of ischemic stroke associated with new-onset atrial fibrillation complicating acute coronary syndrome: A systematic review and meta-analysis

BACKGROUNDnAtrial fibrillation has been established as a major risk factor of ischemic stroke, however, the influence of new-onset atrial fibrillation (NOAF) complicating acute coronary syndrome (ACS) on ischemic stroke remains controversial. This meta-analysis aimed to validate the association between NOAF complicating ACS and ischemic stroke.nnnMETHODSnWe identified randomized controlled trials and cohort studies comparing the ischemic stroke risk between patients with NOAF and sinus rhythm after ACS by searching MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases. We included studies reporting the number of ischemic stroke events or their risk estimates at the longest follow-up. We pooled risk ratios (RRs) using a random-effects model. This meta-analysis is registered in PROSPERO (CRD42017079858).nnnRESULTSnIn the 14 included studies (nu202f=u202f292,774, 5 randomized controlled trials and 9 cohort studies), NOAF was associated with an increased risk of ischemic stroke (RR: 2.84, 95% confidence interval [CI]: 1.91-4.23; 6 studies), especially for patients with ST-segment elevation myocardial infarction (RR: 4.01, 95% CI: 2.61-6.18; 3 studies). In addition, the detrimental impact persisted in patients with transient NOAF (RR: 3.05, 95% CI: 1.63-5.70; 3 studies). The pooled result from a sensitivity analysis in which all individual components in the CHA2DS2-VASc score (heart failure, hypertension, age, diabetes, previous stroke, vascular disease and female sex) had been adjusted further validated the association between NOAF and ischemic stroke (RR: 2.32, 95% CI: 1.53-3.52; 4 studies).nnnCONCLUSIONSnNOAF is significantly associated with ischemic stroke events in patients with ACS, even after adjustment for several important ischemic stroke risk factors.

Lipid oxidation inactivates the anticoagulant function of Protein Z-Dependent Protease Inhibitor (ZPI)

Lipid oxidation due to oxidative stress plays an important role in the pathogenesis of inflammatory and thrombotic cardiovascular diseases. Several findings suggest that lipid peroxidation can alter the function of coagulation proteins and contribute to a hypercoagulable state, but the molecular mechanisms are unclear. Here, we report that oxidized phospholipids suppress the anticoagulant function of the serpin, protein Z-dependent protease inhibitor (ZPI), a specific inhibitor of membrane-associated factor Xa (FXa) that requires protein Z (PZ), phospholipid, and calcium as cofactors. We found that this suppression arises from a diminished ability of the oxidized membrane to function as a cofactor to promote ZPI inhibition of membrane-bound FXa, due fully or in part to the susceptibility of the bound ZPI-PZ complex to oxidative inactivation. Surprisingly, free ZPI was also susceptible to inactivation by oxidized membrane vesicles in the absence of calcium. Oxidized vesicles containing both phosphatidylserine and polyunsaturated fatty acids were required to promote inactivation of the ZPI-PZ complex or free ZPI, indicating that binding of the PZ-complexed or free ZPI to peroxide-modified phospholipid vesicles mediates the inactivation. Heparin protected the ZPI-PZ complex and free ZPI from inactivation, suggesting that blocking the heparin-binding site on ZPI interferes with ZPI binding to lipid or to PZ. This was confirmed by direct lipid-binding experiments. Native PAGE indicated that oxidization induced dissociation of the ZPI-PZ complex and increased the negative charge of ZPI. We conclude that compromised ZPI anticoagulant function could contribute to thrombus initiation and growth in oxidative stress-induced cardiovascular diseases.

Risk evaluation of new-onset atrial fibrillation complicating ST-segment elevation myocardial infarction: a comparison between GRACE and CHA 2 DS 2 -VASc scores

Purpose New-onset atrial fibrillation (NOAF) is a common finding in patients with myocardial infarction (MI), but few studies are available regarding the prediction model for its risk estimation. Although Global Registry of Acute Coronary Events (GRACE) risk score (RS) has been recognized as an effective tool for the risk evaluation of clinical outcomes in patients with MI, its usefulness in the prediction of post-MI NOAF remains unclear. In this study, we sought to validate the discrimination performance of GRACE RS in the prediction of post-MI NOAF and to make a comparison with that of the CHA2DS2-VASc score in patients with ST-segment elevation myocardial infarction (STEMI). Patients and methods A total of 488 patients with STEMI who were admitted to our hospital between May 2015 and October 2016 without a history of atrial fibrillation were retrospectively evaluated in this study. GRACE and CHA2DS2-VASc scores were calculated for each patient. Patients were divided into low (GRACE RS≤125)-, intermediate (GRACE RS 126–154)-, and high (GRACE RS≥155)-risk groups. Receiver operating characteristic curve analyses were performed to evaluate the discrimination performance of both RSs. Model calibration was evaluated by using Hosmer–Lemeshow goodness-of-fit test (HLS). Results Of the 488 eligible patients, 49 (10.0%) developed NOAF during hospitalization. In the overall cohort, the discrimination performance of GRACE RS (C-statistic: 0.76, 95% CI: 0.72–0.80) was significantly better than that of CHA2DS2-VASc score (C-statistic: 0.68, 95% CI: 0.64–0.72; comparison p=0.03). For subgroup analysis, GRACE RS tended to be better than the CHA2DS2-VASc score in all but the intermediate-risk group as evidenced by C-statistics of 0.60 and 0.65 for GRACE and CHA2DS2-VASc scores, respectively. Excellent calibration was achieved except for GRACE RS in females (HLS p=0.05). Conclusion The diagnostic performance of GRACE RS is relatively high as well as better than that of the CHA2DS2-VASc score with respect to the prediction of post-MI NOAF.

Saponin extract from Panax notoginseng promotesangiogenesis through AMPK‑ and eNOS‑dependent pathways in HUVECs

Panax notoginseng saponins (PNS) are among the most important compounds extracted from Panax notoginseng root, and have long been used in traditional Chinese medicine to control bleeding. PNS have recently garnered attention for the treatment of circulatory system diseases. The present study aimed to evaluate the effects of PNS on angiogenesis in vitro and to explore the molecular mechanisms underlying their actions. The present results demonstrated that the proliferative ability of human umbilical vein endothelial cells (HUVECs) was augmented following treatment with PNS. In addition, wound healing and Boyden chamber assays indicated that PNS may enhance HUVEC motility and increase the number of capillary-like tube branches in HUVECs. These effects were suppressed by 5′ adenosine monophosphate-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) inhibitors. Furthermore, western blot analysis demonstrated that PNS stimulated the phosphorylation of AMPK and eNOS at Thr-172 and Ser-1179, respectively. These results suggested that PNS may promote tube formation in endothelial cells through AMPK- and eNOS-dependent signaling pathways.

Does left atrial appendage (LAA) occlusion device alter the echocardiography and electrocardiogram parameters in patients with atrial fibrillation

BACKGROUNDnThe alterations of echocardiography and electrocardiogram (ECG) in patients received left atrial appendage LAA occlusion therapy are still unclear. The present study was to evaluate the influence of LAA occlusion device on echocardiography and ECG changes in patients with atrial fibrillation (AF).nnnMETHODSnSeventy-three patients who had undergone Watchman, LAmbre and Lefort were enrolled in this study. Echocardiography and ECG results at pre- and post-operation were collected. Besides, echocardiography was also performed during follow-up visits at 1, 6 and 12months after discharge.nnnRESULTSnAfter LAA occlusion, a slight and measureable movement of QRS electric axis was observed in most patients. The significant differences were also observed in heart rate (HR) and the mean-mean QT interval between pre- and post-operation for all patients. There existed no significant difference in echocardiographic parameters between before and after device implantation. However, a larger left atrial (LA) diameter was detected by echocardiography during follow-up visit at 6months when compared with pre-operation parameters. Similarly, aortic root diameter (ARD) was also larger during follow-up at 12months than the baseline dimension in pre-operation.nnnCONCLUSIONSnLAA occlusion device resulted in a slightly movement in QRS axis, reduced HR and increased the mean-mean QT interval duration. In addition, LA diameter and ARD seemed to be larger after device implantation.