Dachun Xu

Fudan University, Shanghai, Shanghai Shi, China

Are you Dachun Xu?

Claim your profile

Publications (11)42.22 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Increased pulmonary arterial smooth muscle cells (PASMCs) proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Isorhynchophylline (IRN) is a tetracyclic oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla. It has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether IRN can influence the development of PAH. Here we examined the effect of IRN on monocrotaline (MCT) induced PAH in rats. Our data demonstrated that IRN prevented MCT induced PAH in rats, as assessed by right ventricular (RV) pressure, the weight ratio of RV to (left ventricular + septum) and RV hypertrophy. IRN significantly attenuated the percentage of fully muscularized small arterioles, the medial wall thickness, and the expression of smooth muscle α-actin (α-SMA) and proliferating cell nuclear antigen (PCNA). In vitro studies, IRN concentration-dependently inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of PASMCs. Fluorescence-activated cell-sorting analysis showed that IRN caused G0/G1 phase cell cycle arrest. IRN-induced growth inhibition was associated with downregulation of cyclin D1 and CDK6 as well as an increase in p27Kip1 levels in PDGF-BB-stimulated PASMCs. Moreover, IRN negatively modulated PDGF-BB-induced phosphorylation of PDGF-Rβ, ERK1/2, Akt/GSK3β, and signal transducers and activators of transcription 3 (STAT3). These results demonstrate that IRN could inhibit PASMCs proliferation and attenuate pulmonary vascular remodeling after MCT induction. These beneficial effects were at least through the inhibition of PDGF-Rβ phosphorylation and its downstream signaling pathways. Therefore, IRN might be a potential candidate for the treatment of PAH.
    Biochemical and Biophysical Research Communications 06/2014; · 2.28 Impact Factor
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Edoxaban, a factor Xa inhibitor, is a new oral anticoagulant that has been developed as an alternative to vitamin K antagonists. However, its safety remains unexplored. Medline, Embase and Web of Science were searched to March 8, 2014 for prospective, randomized controlled trials (RCTs) that assessed the safety profile of edoxaban with warfarin. Safety outcomes examined included bleeding risk and mortality. Five trials including 31,262 patients that met the inclusion criteria were pooled. Overall, edoxaban was associated with a significant decrease in major or clinically relevant nonmajor bleeding events [risk ratio (RR) 0.78, 95% confidence interval (CI) 0.74 to 0.82, p<0.001] and any bleeding events [RR 0.82, 95% CI 0.79 to 0.85, p<0.001]. Edoxaban also showed superiority to warfarin both in all-cause mortality [RR 0.92, 95% CI0.85 to0.99, p = 0.02] and cardiovascular mortality [RR 0.87, 95% CI0.79 to 0.96, p = 0.004]. Subgroup analyses indicated that RRs of edoxaban 30, 60 or 120 mg/d were 0.67 (p<0.001), 0.87 (p<0.001) and 3.3 (p = 0.004) respectively in major or clinically relevant nonmajor bleeding; 0.71 (p<0.001), 0.89 (p<0.001) and 2.29 (p = 0.002) respectively in any bleeding; as well as 0.86 (p = 0.01), 0.87 (p = 0.01) and 0.28 (p = 0.41) respectively in cardiovascular death… Meanwhile, paramount to note that pooled results other than the largest trial showed edoxaban was still associated with a decrease in the rate of major or clinically relevant nonmajor bleeding event (p = 0.02) and any bleeding (p = 0.002), but neither in all-cause death (p = 0.66) nor cardiovascular death (p = 0.70). Edoxaban, a novel orally available direct factor Xa inhibitor, seems to have a favorable safety profiles with respect to bleeding risk and non-inferior in mortality when compared to warfarin. Further prospective RCTs are urgently needed to confirm the results of this meta-analysis.
    PLoS ONE 01/2014; 9(4):e95354. · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In response to several stresses, including nutrient deprivation, general control nonderepressible 2 kinase (GCN2) attenuates mRNA translation by phosphorylating eukaryotic initiation factor 2α(Ser51). Energy starvation is known to exacerbate congestive heart failure, and eukaryotic initiation factor 2α(Ser51) phosphorylation is increased in the failing heart. However, the effect of GCN2 during the evolution of congestive heart failure has not been tested. In this study, we examined the influence of GCN2 expression in response to a cardiac stress by inducing chronic pressure overload with transverse aortic constriction in wild-type and GCN2 knockout mice. Under basal conditions, GCN2 knockout mice had normal left ventricular structure and function, but after transverse aortic constriction, they demonstrated less contractile dysfunction, less increase in lung weight, less increase in lung inflammation and vascular remodeling, and less myocardial apoptosis and fibrosis compared with wild-type mice, despite an equivalent degree of left ventricular hypertrophy. As expected, GCN2 knockout attenuated transverse aortic constriction-induced cardiac eukaryotic initiation factor 2α(Ser51) phosphorylation and preserved sarcoplasmic reticulum Ca(2+) ATPase expression compared with wild-type mice. Interestingly, the expression of the antiapoptotic protein Bcl-2 was significantly elevated in GCN2 knockout hearts, whereas in isolated neonatal cardiomyocytes, selective knockdown of GCN2 increased Bcl-2 protein expression and enhanced myocyte resistance to an apoptotic stress. Collectively, our data support the notion that GCN2 impairs the ventricular adaptation to chronic pressure overload by reducing Bcl-2 expression and increasing cardiomyocyte susceptibility to apoptotic stimuli. Our findings suggest that strategies to reduce GCN2 activity in cardiac tissue may be a novel approach to attenuate congestive heart failure development.
    Hypertension 10/2013; · 6.87 Impact Factor
  • International journal of cardiology 07/2013; · 6.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: : The effects of differences among β-blockers and initiation times in patients undergoing noncardiac surgery (NCS) remain unknown. On June 1, 2012, the authors searched PubMed, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials to identify all trials of perioperative β-blockers in patients undergoing NCS published between January 1960 and June 2012. The authors included only randomized, double-blind and placebo-controlled trials of perioperatively administered β-blockers (ie, during the pre-, intra- and/or postoperative period) in patients with at least 1 risk factor for coronary artery disease undergoing NCS. The endpoints of these trials had to include all-cause mortality, myocardial infarction (MI) and/or stroke. The authors identified 8 English-language publications, involving 11,180 patients, which fulfilled our inclusion criteria. Perioperative β-blocker therapy was associated with a significant decrease in patient risk of developing MI (relative risk [RR] = 0.73; 95% confidence interval [CI], 0.61-0.86) but a significant increase in risk of developing stroke (RR = 2.17; 95% CI, 1.35-3.50) versus placebo, resulting in a nonsignificant decrease in overall mortality (RR = 0.91; 95% CI, 0.60-1.36). Indirect comparisons demonstrated that perioperative atenolol therapy was associated with lower mortality and incidence of MI. β-blocker therapy initiated >1 week before surgery was associated with improved postoperative mortality. Perioperative β-blocker treatment of patients undergoing NCS increases the incidence of stroke but decreases the incidence of MI, leading to a nonsignificant decrease in mortality. The authors also observed that atenolol treatment or β-blocker therapy initiated >1 week before NCS was associated with improved outcomes.
    The American Journal of the Medical Sciences 04/2013; · 1.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Blood pressure (BP) remains poorly controlled among hypertensive patients with coronary heart disease (CHD) in China. Improvement of its management will require an understanding of the patient characteristics and treatment factors associated with uncontrolled hypertension. A cross-sectional survey of 3,279 patients from 52 centers in China was performed to examine potential barriers to adequate blood pressure control of hypertensive patients with CHD. Uncontrolled hypertension was defined as blood pressure ≥130/or 80 mmHg. Multivariable logistic regression was used to identify factors associated with poor blood pressure control. Mean age of the patients was 65 years, 40% were women, and mean BMI was 25 kg/m(2). Mean systolic blood pressure was 136±18 mmHg and mean diastolic blood pressure was 80±11 mmHg. Only 18% of patients had a mean blood pressure <130/80 mmHg during the study period. Multivariate analysis revealed several independent factors of poor blood pressure control: body mass index ≥23 kg/m(2), the presence of stable angina pectoris (SAP), family history of diabetes, and use of calcium channel blockers (CCB). Further analysis showed that non-dihydropyridine calcium antagonist was significantly correlated with low BP control rate. Some of these may be amenable to modification. The results of our study suggest that overweight, the presence of SAP and family history of diabetes are important factors for tight BP control in primary care. In addition, non-dihydropyridine calcium channel blockers appear less effective than other therapies in control of blood pressure and should not be the first choice among hypertensive patients with CHD. Further identification of patients at risk of poor BP control can lead to targeted interventions to improve management.
    PLoS ONE 01/2013; 8(5):e63135. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: In a previous review, we reported that ankle brachial index (ABI) ≤ 0.90 could reliably identify patients with peripheral artery disease (PAD). Since then, more studies have been published which may extend the power of a meta-analysis of studies of diagnostic accuracy of the ABI. MEDLINE and several other databases were searched for studies on sensitivity and specificity of using ABI ≤ 0.90 for PAD diagnosis compared with angiography. METHODS: Quality of each study was assessed by standards for reporting diagnostic accuracy initiative and quality assessment for studies of diagnostic accuracy tool. Heterogeneity was assessed using the Cochran Q statistic, χ(2), and inconsistency index. The area under the curve and Q* were estimated using summary receiver operator curve. The pooled diagnostic odds ratio (DOR), sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of ABI ≤ 0.90 to diagnose PAD were estimated using Meta-DiSc software (Meta-DiSc, Madrid, Spain). RESULTS: Four studies comprising 569 patients (922 limbs) met inclusion criteria. Significant heterogeneity among these studies was not detected in DOR but was evident in pooled sensitivity, specificity, PLR, and NLR. The area under the curve under the summary receiver operator curve is 0.87 (standard error = 0.02) and diagnostic accuracy (Q*) is 0.80 (standard error = 0.02). Additionally, DOR was 15.33 with corresponding 95% confidence intervals of 9.39-25.02. The pooled sensitivity and specificity of ABI ≤ 0.90 for PAD diagnosis were 75% and 86% and the pooled PLR and NLR were 4.18 and 0.29, respectively. CONCLUSIONS: We conclude that test of ABI ≤ 0.90 can be a useful tool to identify PAD with serious stenosis in clinical practice.
    The Canadian journal of cardiology 08/2012; · 3.12 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic left ventricular failure causes pulmonary congestion with increased lung weight and type 2 pulmonary hypertension. Understanding the molecular mechanisms for type 2 pulmonary hypertension and the development of novel treatments for this condition requires a robust experimental animal model and a good understanding of the nature of the resultant pulmonary remodeling. Here we demonstrate that chronic transverse aortic constriction causes massive pulmonary fibrosis and remodeling, as well as type 2 pulmonary hypertension, in mice. Thus, aortic constriction-induced left ventricular dysfunction and increased left ventricular end-diastolic pressure are associated with a ≤5.3-fold increase in lung wet weight and dry weight, pulmonary hypertension, and right ventricular hypertrophy. Interestingly, the aortic constriction-induced increase in lung weight was not associated with pulmonary edema but resulted from profound pulmonary remodeling with a dramatic increase in the percentage of fully muscularized lung vessels, marked vascular and lung fibrosis, myofibroblast proliferation, and leukocyte infiltration. The aortic constriction-induced left ventricular dysfunction was also associated with right ventricular hypertrophy, increased right ventricular end-diastolic pressure, and right atrial hypertrophy. The massive lung fibrosis, leukocyte infiltration, and pulmonary hypertension in mice after transverse aortic constriction clearly indicate that congestive heart failure also causes severe lung disease. The lung fibrosis and leukocyte infiltration may be important mechanisms in the poor clinical outcome in patients with end-stage heart failure. Thus, the effective treatment of left ventricular failure may require additional efforts to reduce lung fibrosis and the inflammatory response.
    Hypertension 04/2012; 59(6):1170-8. · 6.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Studies have demonstrated that increased oxidative stress contributes to the pathogenesis and the development of pulmonary artery hypertension (PAH). Extracellular superoxide dismutase (SOD3) is essential for removing extracellular superoxide anions, and it is highly expressed in lung tissue. However, it is not clear whether endogenous SOD3 can influence the development of PAH. Here we examined the effect of SOD3 knockout on hypoxia-induced PAH in mice and a loss-of-function SOD3 gene mutation (SOD3(E124D)) on monocrotaline (40 mg/kg)-induced PAH in rats. SOD3 knockout significantly exacerbated 2 weeks of hypoxia-induced right ventricular (RV) pressure and RV hypertrophy, whereas RV pressure in SOD3 knockout mice under normoxic conditions is similar to wild-type controls. In untreated control rats at age of 8 weeks, there was no significant difference between wild-type and SOD3(E124D) rats in RV pressure and the ratio of RV weight:left ventricular weight (0.25±0.02 in wild-type rats versus 0.25±0.01 in SOD3(E124D) rats). However, monocrotaline caused significantly greater increases of RV pressure in SOD3(E124D) rats (48.6±1.8 mm Hg in wild-type versus 57.5±3.1 mm Hg in SOD3(E124D) rats), of the ratio of RV weight:left ventricular weight (0.41±0.01 versus 0.50±0.09; P<0.05), and of the percentage of fully muscularized small arterioles in SOD3(E124D) rats (55.2±2.3% versus 69.9±2.6%; P<0.05). Together, these findings indicate that the endogenous SOD3 has no role in the development of PAH under control conditions but plays an important role in protecting the lung from the development of PAH under stress conditions.
    Hypertension 08/2011; 58(2):303-9. · 6.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The ankle-brachial index (ABI) is a simple, inexpensive diagnostic test for peripheral artery disease (PAD). However, it has shown variable accuracy for identification of significant stenosis. The authors performed a structured review of the sensitivity and specificity of ABI ≤ 0.90 for the diagnosis of PAD. MEDLINE, EMBASE, Cochrane databases, Science Citation Index database, and Biological Abstracts database were searched for studies of the sensitivity and specificity of using ABI ≤ 0.90 for the diagnosis of PAD. Eight studies comprising 2043 patients (or limbs) met the inclusion criteria. The result indicated that, although strict inclusion criteria on studies were formulated, different reference standards were found in these studies, and methods of ABI determination and characteristics of populations varied greatly. A high level of specificity (83.3-99.0%) and accuracy (72.1-89.2%) was reported for an ABI ≤ 0.90 in detecting ≥ 50% stenosis, but there were different levels of sensitivity (15-79%). Sensitivity was low, especially in elderly individuals and patients with diabetes. In conclusion, the test of ABI ≤ 0.90 can be a simple and useful tool to identify PAD with serious stenosis, and may be substituted for other non-invasive tests in clinical practice.
    Vascular Medicine 10/2010; 15(5):361-9. · 1.62 Impact Factor

Publication Stats

60 Citations
42.22 Total Impact Points

Institutions

  • 2013
    • Fudan University
      Shanghai, Shanghai Shi, China
  • 2010–2013
    • Tongji Medical University
      • Department of Cardiology
      Shanghai, Shanghai Shi, China
  • 2010–2012
    • Tongji University
      Shanghai, Shanghai Shi, China
  • 2011
    • University of Minnesota Duluth
      Duluth, Minnesota, United States