Aim:This study was designed to characterize the influence of polysaccharide sulfate (PSS),a new type heparinoid extracted from Phylum Phaeophyta,on cardiac function after I/R injury. Methods:Isolated rat hearts were p...
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Aim:This study was designed to characterize the influence of polysaccharide sulfate (PSS),a new type heparinoid extracted from Phylum Phaeophyta,on cardiac function after I/R injury. Methods:Isolated rat hearts were perfused(Langendorff) and subjected to 20 min global ischemia followed by 60 min reperfusion with Kreb's Henseleit solution or PSS(0.3-100 mg/L).Myocardial contractile function was continuously *** kinase(CK) and lactate dehydrogenase(LDH) leakage were *** necrosis factor-α(TNF-α) expression and release by rat hearts was *** addition,Western blot analyses for extracellular regulated kinases(ERKs),c-jun amino-terminal kinase(JNKs) and p38 mitogen-activated protein kinase(MAPK) activity were performed. Results:Cardiac contractility markedly decreased after I/R,consistently with the rise of CK and LDH activity in the coronary effluent,whilst optimal protection of PSS against I/R injury was manifest at concentrations of 1-30 mg/L with improvement of all functional parameters and reduction of CK and LDH *** administration(1-30 mg/L) during reperfusion causes the inhibition of TNF-αprotein production and release from the isolated ischemic rat *** blot analyses showed activated JNK1/2 and p38 increased in I/R rat hearts but diminished in PSS(1-30 mg/L) treated hearts,and phosphorylated-ERK1/2 level was *** contrast,the high concentration of PSS(100 mg/L) had adverse effects that caused worsening of heart function. Conclusions:PSS has cardioprotective effect after I/R injury on the rat heart *** the beneficial effect may be mediated through the MAPK pathway.A diminished inflammatory response may play a role.
Background & objective:High plasma homocysteine(Hcy) levels are associated with coronary artery disease,but the precise level associated with an increased risk is yet *** the beneficial effects of folic acid on ar...
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Background & objective:High plasma homocysteine(Hcy) levels are associated with coronary artery disease,but the precise level associated with an increased risk is yet *** the beneficial effects of folic acid on arterial endothelial function persist over longer periods is not *** study aimed to assess whether folic acid supplementation could produce improvements in Hcy levels and arterial endothelial function in the patients with unstable angina(UA) and ***:The plasma Hcy levels of 52 cases with UA and 30 age and sex-matched control subjects were measured by using high-performance liquid chromatography(HPLC) with fluorescence detection,plasma folic acid and VitB12 levels were measured with *** patients with hyperhomocysteinemia were treated with 5mg of folic acid for 8 weeks,and then rechecked the plasma levels of Hcy,folic acid and VitB 12 at the end of 4th and 8th *** endothelial function was measured as flow-mediated dilation of the brachial artery using high-resolution B-mode ultrasound in 22 cases with UA and hyperhomocysteinemia. Results:The plasma Hcy level was significant higher in the patients with UA than in the controls [(19.2±4.9)μmol/L vs(10.7±5.3)μmol/L,P<0.01].The plasma levels of folic acid and VitB12 were significant lower in the patients with UA than in the controls[(7.0±2.5)μg/L and(586.7±164.5) ng/L vs (5.1±2.0)μg/L and(471.6±135.4) ng/L,all P<0.05].There are 42.3%of the patients with hyperhomocysteinemia in UA *** 4 and 8 weeks of administration of folic acid,the Hcy level reduced by 20.3%and 55.3%in the UA patients with hyperhomocysteinemia,***-mediated dilation also improved significantly,from 6.4%±1.9%to 9.0%±1.2%(P<0.05) after 8-week treatment with folic ***:Hcy level is elevated in patients with *** acid can reduce the plasma Hcy levels and improve arterial endothelial function in the UA patients with hyperhomocysteinemia.
It is well known that angiotensin-(1-7)(Ang-(1-7)) counterbalances vasoconstrictive and proliferative functions of angiotensinⅡ(AngⅡ),some of those actions are via inhibition of AngⅡinduced activation of mitogen-ac...
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It is well known that angiotensin-(1-7)(Ang-(1-7)) counterbalances vasoconstrictive and proliferative functions of angiotensinⅡ(AngⅡ),some of those actions are via inhibition of AngⅡinduced activation of mitogen-activated protein kinases(MAPK).This study investigated the effects of Ang-(1-7) on AngⅡ-mediated cell signaling pathways in mouse bone marrow-derived dendritic cells(DC).The expression of receptor Mas and angiotensin-converting enzyme-related carboxypeptidase(ACE2) mRNA was examined by reverse transcription-polymerase chain reaction(RT-PCR);activation of MAPK was detected by immunoblotting after incubation of dendritic cells with AngⅡin the presence or absence of Ang-(1-7),valsartan,PD123319, and D-Ala7-Ang-(1-7).AngⅡrapidly(5 min,10-7 mol/L) stimulated phosphorylation of extracellular signal-related kinase(ERK1/2);this effect was partially inhibited by AngⅡtype 1(AT1) receptor antagonist valsartan and significantly attenuated by AngⅡtype 2(AT2) receptor antagonist ***-(1-7) alone also induced phosphorylation of ERK1/2;co-treatment of Ang-(1-7) and AngⅡmarkedly enhanced ERK1/2 phosphorylation,the enhancement was eliminated by the Ang-(1-7) receptor antagonist D-Ala7-Ang-(1-7).Both Ang-(1-7) and AngⅡhad no effect on p38 and c-Jun N-terminal kinase(JNK) *** conclusion, AngⅡstimulates ERK1/2 phosphorylation via AT2 receptor in mouse DC,Ang-(1-7) enhances this effect. Generation of Ang-(1-7) by DC could thereby counteract on the proinflammatory function of locally generated AngⅡ.
Background—The congenital long QT syndrome is a heterogeneous genetic disease associated with delayed cardiac repolarization,prolonged electrocardiographic QT intervals,the development of ventricular arrhythmias(tors...
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Background—The congenital long QT syndrome is a heterogeneous genetic disease associated with delayed cardiac repolarization,prolonged electrocardiographic QT intervals,the development of ventricular arrhythmias(torsades de pointes) and sudden *** 2 congenital long-QT syndrome(LQT2) results from KCNH2 or human ether-a-go-go related gene(hERG) *** KCNH2 encodes the Kv11.1α-subunit of the rapidly activating delayed rectifier K- current(IKr) in the *** of mutant hERG channels in heterologous systems indicate that most LQT2 missense mutations generate trafficking-deficient Kv11.1 *** aim of this study is to use molecular and electrophysiological analyses to identify the mechanism underlying G572R. Methods and Results—To elucidate the electrophysiological properties of the G572R mutant channels,Mutant hERG subunits were heterologously expressed in HEK293 cells alone or in combination with wild-type(WT) hERG ***-clamp techniques were used to record currents,and a enhanced green fluorescent protein tagging and Western blot analyses were performed to examine the cellular trafficking of mutant *** expressed alone,G572R subunits were not present in the cell membrane,and did not induce detectable *** of mutant and WT hERG subunits caused a dominant-negative effect.G572R channels had a trafficking-deficient phenotype. Conclusion—A novel KCNH2 missense mutation,G572R,causing the substitution of a glycine with an arginine residue at position 572,located at the end of the S5 transmembrane segment of the hERG(IKr) -*** genetic lesion produces a completely non-functional ion channel protein that interferes with WT channel protein and,likes most LQT2 missense mutations,do not traffic to the plasma membrane.
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