[Show abstract][Hide abstract] ABSTRACT: The rapidly activating delayed rectifier potassium current (IKr) plays a critical role in cardiac repolarization. Although IKr is known to be regulated by both α1- and β1-adrenergic receptors (ARs), the cross-talk and feedback mechanisms that dictate its response to α1- and β1-AR activation are not known. In the present study, IKr was recorded using the whole-cell patch-clamp technique. IKr amplitude was measured before and after the sequential application of selective adrenergic agonists targeting α1- and β1-ARs. Stimulation of either receptor alone (α1-ARs using 1 μM phenylephrine (PE) or β1-ARs using 10 μM xamoterol (Xamo)) reduced IKr by 0.22 ± 0.03 and 0.28 ± 0.01, respectively. The voltage-dependent activation curve of IKr shifted in the negative direction. The half-maximal activation voltage (V0.5) was altered by -6.35 ± 1.53 and -1.95 ± 2.22 mV, respectively, with no major change in the slope factor (k). When myocytes were pretreated with Xamo, PE-induced reduction in IKr was markedly blunted and the corresponding change in V0.5 was significantly altered. Similarly, when cells were pretreated with PE, Xamo-induced reduction of IKr was significantly attenuated. The present results demonstrate that functional cross-talk between α1- and β1-AR signaling regulates IKr. Such non-linear regulation may form a protective mechanism under excessive adrenergic stimulation.
International Journal of Molecular Sciences 08/2014; 15(8):14220-33. · 2.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine the association between hemoglobin (Hb) levels and cardiovascular risk factors in a large community-dwelling cohort.
A total of 4,186 women and 4,851 men were enrolled in the study. Data on personal history, physical examination and biochemical parameters were collected. Subjects were categorized by gender and divided into different group according to the level of Hb or blood pressure, and the association between Hb levels and cardiovascular risk factors was examined using Pearson's correlation analysis.
In both men and women even with normal Hb level, tertiles of Hb levels were positively associated with body mass index (BMI), total-cholesterol (TC), triglyceride (TG), uric acid (UA), diastolic blood pressures (DBP) and fasting plasma glucose (FPG) (all P=0.000 in men and women). Furthermore, significantly increased incidence of hyperuricemia (P=0.000 both in men and women) and obesity (P=0.000 both in men and women) were observed with the gradually increased Hb level. In addition, Pearson's correlation analysis revealed obvious correlation between Hb level and various cardiovascular risk factors including blood pressure and UA. Binary logistic regression analysis further demonstrated that the level of Hb was an important risk factor for elevated blood pressure (OR =1.216; 95% CI: 1.138-1.293, P=0.000 in men; OR =1.287; 95% CI: 1.229-1.363, P=0.000 in women).
Increasing Hb levels, even in subjects with normal level were associated with increasing prevalence of cardiovascular risk factors, suggesting that a slightly low Hb level might be beneficial to Chinese community-dwelling individuals.
Journal of thoracic disease. 05/2014; 6(5):477-82.
[Show abstract][Hide abstract] ABSTRACT: To explore the long-term effects and pain relief mechanism of acupotomy by observing changes in nitric oxide synthase (NOS) and beta-endorphin (beta-EP) in the hypothalamus, spinal cord, and peripheral blood of rats with third lumbar vertebrae (L3) transverse process syndrome.
Twenty-eight SD rats were randomly assigned to normal, model, electroacupuncture (EA), and acupotomy group. The last three groups were put through an operation to emulate L3 transverse process syndrome. Fourteen days after the simulation operation, EA and acupotomy treatments were applied to the respective groups. Fifty-six days after the simulation operation, biochemistry tests and enzyme-linked immunosorbent assay were used to measure NOS and beta-EP in the hypothalamus, spinal cord, and peripheral blood.
Rats with the simulation operation showed significantly higher levels of NOS and beta-EP in the hypothalamus, spinal cord, and peripheral blood than those in the normal group. The EA and acupotomy groups had significantly lower levels of NOS and beta-EP than those in the model group. There was no statistical difference between the EA and acupotomy groups.
EA and acupotomy treatments significantly lowered NOS and beta-EP levels in the hypothalamus, spinal cord, and peripheral blood and alleviated L3 transverse process syndrome.
Journal of Traditional Chinese Medicine 04/2014; 34(2):194-8. · 0.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human ether‑à‑go‑go‑related gene (hERG) potassium channels conduct the rapid component of the delayed rectifier potassium current (IKr), which is crucial for repolarization of cardiac action potential. Patients with hERG‑associated long QT syndrome usually develop tachyarrhythmias during physical and/or emotional stress, both known to stimulate adrenergic receptors. The present study aimed to investigate a putative functional link between β1‑adrenergic stimulation and IKr in guinea‑pig left ventricular myocytes and to analyze how IKr is regulated following activation of the β1‑adrenergic signaling pathway. The IKr current was measured using a whole‑cell patch‑clamp technique. A selective β1‑adrenergic receptor agonist, xamoterol, at concentrations of 0.01‑100 µM decreased IKr in a concentration‑dependent manner. The 10 µM xamoterol‑induced inhibition of IKr was attenuated by the protein kinase A (PKA) inhibitor KT5720, the protein kinase C (PKC) inhibitor chelerythrine, and the phospholipase (PLC) inhibitor U73122, indicating involvement of PKA, PKC and PLC in β1‑adrenergic inhibition of IKr. The results of the present study indicate an association between IKr and the β1‑adrenergic receptor in arrhythmogenesis, involving the activation of PKA, PKC and PLC.
Molecular Medicine Reports 03/2014; · 1.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: No available prognostic factor was identified for atherosclerotic renovascular stenosis (ARAS) patient who undergo the percutaneous revascularization therapy.
This is a case of 68-year-old ARAS patient associated with hypertension and massive proteinuria, who exhibited progressive aggravation of renal dysfunction. His proteinuria selectivity index (SI) was only 0.08. Then the stenosis was treated by percutaneous transluminal angioplasty of the renal artery (PTRA) and stenting. After 2-year follow up, all symptoms including renal dysfunction and uncontrolled hypertension was well-controlled.
As no reliable predictors of clinical response have been identified yet, SI might be a simple prognositic index for ARAS patients undergone the revascularzation therapy.
Journal of thoracic disease. 08/2013; 5(4):E158-61.
[Show abstract][Hide abstract] ABSTRACT: Atorvastatin is postulated to improve arterial stiffness in patients with diabetes mellitus or hypercholesterolemia; however, in elderly hypertensive patients, its effect on arterial stiffness and the possible mechanisms are unknown. A total of 73 elderly hypertensive patients were enrolled to receive atorvastatin for 6 months. Brachial-ankle pulse wave velocity (baPWV) and circulating biomarkers were measured before and after the intervention. After 6 months of treatment, the patients experienced a 19.66% reduction in low-density lipoprotein cholesterol (2.90±0.58 vs 2.33±0.56 mmol/L, P<.01) and a 10.63% reduction in baPWV (2100.89±513.21 vs 1877.56±432.06 cm/s, P=.01). In addition, a 21.79% reduction in circulating N-(epsilon)-carboxymethyl-lysine and a 20% reduction in Von Willebrand factor level were observed after treatment. Meanwhile, the activity of copper/zinc-containing superoxide dismutase (Cu/Zn SOD) was increased by 26.64% (5.04±1.01 vs 6.87±1.83 U/L, P<.001). Correlation analysis demonstrated that the increase of Cu/Zn SOD activity was related to the reductions of arterial stiffness (r=-0.340, P=.003). Taken together, these findings suggest that atorvastatin can improve arterial stiffness possibly by reducing oxidative stress levels in elderly hypertensive patients.
Journal of Clinical Hypertension 04/2012; 14(4):245-9. · 2.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to make use of the artificially induced aging model cardiomyocytes to further investigate potential anti-aging-associated cellular diastolic dysfunction effects of EGB761 and explore underlying molecular mechanisms. Cultured rat primary cardiomyocytes were treated with either D-galactose or D-galactose combined with EGB761 for 48 h. After treatment, the percentage of cells positive for SA-β-gal, AGEs production, cardiac sarcoplasmic reticulum calcium pump (SERCA) activity, the myocardial sarcoplasmic reticulum calcium uptake, and relative protein levels were measured. Our results demonstrated that in vitro stimulation with D-galactose induced AGEs production. The addition of EGB761 significantly decreased the number of cells positive for SA-β-gal. Furthermore, decreased diastolic [Ca(2+)](i), curtailment of the time from the maximum concentration of Ca(2+) to the baseline level and increased reuptake of Ca(2+) stores in the SR were also observed. In addition, the level of p-Ser16-PLN protein as well as SERCA was markedly increased. The study indicated that EGb761 alleviates formation of AGEs products on SERCA2a in order to mitigate myocardial stiffness on one hand; on other hand, improve SERCA2a function through increase the amount of Ser16 sites PLN phosphorylation, which two hands finally led to ameliorate diastolic dysfunction of aging cardiomyocytes.
Oxidative Medicine and Cellular Longevity 01/2012; 2012:418748.
[Show abstract][Hide abstract] ABSTRACT: Metabolic syndrome (MetS) is regarded as a risk factor for coronary artery disease (CAD). But the influence of MetS on morbidity and mortality after stent implantation in CAD patients remains unknown.
This article presents a meta-analysis of available data on the association between the MetS and the risk of angiographic and clinical outcomes following stent implantation.
MetS was associated with a significant increased risk of post-stent all-cause mortality (odd ratio (OR), 2.17, 95% CI, 1.56-3.01), in-lesion restenosis (OR, 1.35, 95% CI, 1.00-1.84) and major adverse cardiac events (MACE) (OR 1.35, 95% CI 1.13-1.61) in CAD patients. Even with drug-eluting stent (DES) implantation, significant increased risk in all-cause mortality (OR, 2.25, 95% CI, 1.61-3.15) and MACE (OR 1.42, 95% CI 1.14-1.76) were remain in patients with MetS. However, the OR of cardiovascular (CV) mortality (1.25, 95% CI 0.71-2.22), MI (1.27, 95% CI 0.87-1.85) and TLR (OR 1.21, 95% CI 0.96-1.53) was not statistically different between the patients with and without metabolic syndrome.
Metabolic syndrome is an important risk factor in patients with CAD following stent implantation. Although DES implantation decreased the incidence of angiographic events, further progress in adequate treatment of MetS is still required to improve the clinical outcome.
[Show abstract][Hide abstract] ABSTRACT: The literature provides no clear answer as to whether matrix metalloproteinases (MMPs) polymorphisms increases risk of myocardial infarction (MI).
Our purpose was to help clarify the inconsistent findings of MMPs polymorphisms and MI susceptibility and identify which MMP polymorphism might play an active role in the occurrence of MI.
Articles were identified by a Medline search and citation tracking.
Eligible articles were case-control studies of MMPs polymorphisms and MI which met our prespecified criteria.
Data were independently extracted by two authors according to a predefined protocol. Incongruities were settled by consensus decision.
18 potentially eligible articles were identified. In a combined analysis, the 5A allele of the MMP-3 5A/6A polymorphism was associated with MI (OR 1.21, 95% CI 1.01 to 1.46, p=0.04), suggesting its role in plaque rupture. In the subgroup analysis by ethnicity, significantly increased risk was found among East Asians (OR 1.39, 95% CI 1.01 to 1.91, p=0.04), whereas no significant association was detected in Caucasian populations. In addition, there were significant associations of the MMP-9 -1562C→T polymorphism with MI (OR 1.14, 95% CI 1.02 to 1.27, p=0.02), whereas the heterogeneity of the studies showed no significance (I(2)=13.7%, p=0.32). This meta-analysis demonstrated that the MMP-3 5A/6A and MMP-9 -1562 C→T polymorphisms are risk factors associated with increased MI susceptibility, but these associations vary in different ethnic populations.
[Show abstract][Hide abstract] ABSTRACT: To investigate the possible effects of alagebrium chloride (ALT-711) on oxidative stress (OS) process in aging hearts, we examined the role of ALT-711 in cardiac function and OS in the heart of aging rats. Increased mitochondrial DNA (mtDNA) deletion as well as nearly a twofold increase in advanced glycation end products (AGEs) accumulation were observed in aging heart, whereas only about 50% of the superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities were seen. However, after treatment with ALT-711, preserved cardiac diastolic function accompanied with reduced mtDNA deletion and about 30% of AGEs decrease was observed in aging hearts. In addition, ALT-711 can increase SOD and GSH-PX activities in aging hearts as well as in cultured cardiomyocytes. In conclusion, our study suggests that AGEs accumulation and the abnormalities in the OS in aging hearts can be attenuated by ALT-711, and this might be a novel underlying mechanism for ALT-711 in the treatment of cardiovascular diseases that develop with aging.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 04/2009; 64(6):629-35. · 4.31 Impact Factor