Identification of molecular subtypes of coronary artery disease based on ferroptosis- and necroptosis-related genes.

Aim: Coronary artery disease (CAD) is a heterogeneous disorder with high morbidity, mortality, and healthcare costs, representing a major burden on public health. Here, we aimed to improve our understanding of the genetic drivers of ferroptosis and necroptosis and the clustering of gene expression in CAD in order to develop novel personalized therapies to slow disease progression. Methods: CAD datasets were obtained from the Gene Expression Omnibus. The identification of ferroptosis- and necroptosis-related differentially expressed genes (DEGs) and the consensus clustering method including the classification algorithm used km and distance used spearman were performed to differentiate individuals with CAD into two clusters (cluster A and cluster B) based expression matrix of DEGs. Next, we identified four subgroup-specific genes of significant difference between cluster A and B and again divided individuals with CAD into gene cluster A and gene cluster B with same methods. Additionally, we compared differences in clinical information between the subtypes separately. Finally, principal component analysis algorithms were constructed to calculate the cluster-specific gene score for each sample for quantification of the two clusters. Results: In total, 25 ferroptosis- and necroptosis-related DEGs were screened. The genes in cluster A were mostly related to the neutrophil pathway, whereas those in cluster B were mostly related to the B-cell receptor signaling pathway. Moreover, the subgroup-specific gene scores and CAD indices were higher in cluster A and gene cluster A than in cluster B and gene cluster B. We also identified and validated two genes showing upregulation between clusters A and B in a validation dataset. Conclusion: High expression of CBS and TLR4 was related to more severe disease in patients with CAD, whereas LONP1 and HSPB1 expression was associated with delayed CAD progression. The identification of genetic subgroups of patients with CAD may improve clinician knowledge of disease pathogenesis and facilitate the development of methods for disease diagnosis, classification, and prognosis.

Single-Cell Sequencing Analysis and Multiple Machine Learning Methods Identified G0S2 and HPSE as Novel Biomarkers for Abdominal Aortic Aneurysm.

Identifying biomarkers for abdominal aortic aneurysms (AAA) is key to understanding their pathogenesis, developing novel targeted therapeutics, and possibly improving patients outcomes and risk of rupture. Here, we identified AAA biomarkers from public databases using single-cell RNA-sequencing, weighted co-expression network (WGCNA), and differential expression analyses. Additionally, we used the multiple machine learning methods to identify biomarkers that differentiated large AAA from small AAA. Biomarkers were validated using GEO datasets. CIBERSORT was used to assess immune cell infiltration into AAA tissues and investigate the relationship between biomarkers and infiltrating immune cells. Therefore, 288 differentially expressed genes (DEGs) were screened for AAA and normal samples. The identified DEGs were mostly related to inflammatory responses, lipids, and atherosclerosis. For the large and small AAA samples, 17 DEGs, mostly related to necroptosis, were screened. As biomarkers for AAA, G0/G1 switch 2 (G0S2) (Area under the curve [AUC] = 0.861, 0.875, and 0.911, in GSE57691, GSE47472, and GSE7284, respectively) and for large AAA, heparinase (HPSE) (AUC = 0.669 and 0.754, in GSE57691 and GSE98278, respectively) were identified and further verified by qRT-PCR. Immune cell infiltration analysis revealed that the AAA process may be mediated by T follicular helper (Tfh) cells and the large AAA process may also be mediated by Tfh cells, M1, and M2 macrophages. Additionally, G0S2 expression was associated with neutrophils, activated and resting mast cells, M0 and M1 macrophages, regulatory T cells (Tregs), resting dendritic cells, and resting CD4 memory T cells. Moreover, HPSE expression was associated with M0 and M1 macrophages, activated and resting mast cells, Tregs, and resting CD4 memory T cells. Additional, G0S2 may be an effective diagnostic biomarker for AAA, whereas HPSE may be used to confer risk of rupture in large AAAs. Immune cells play a role in the onset and progression of AAA, which may improve its diagnosis and treatment.

Skin transcriptome analysis identifies the key genes underlying fur development in Chinese Tan sheep in the birth and Er-mao periods.

Hair follicle development in Tan sheep differs significantly between the birth and Er-mao periods, but the underlying molecular mechanism is still unclear. We profiled the skin transcriptomes of Tan sheep in the birth and Er-mao periods via RNA-seq technology. The Tan sheep examined consisted of three sheep in the birth period and three sheep in the Er-mao period. A total of 364 differentially expressed genes (DEGs) in the skin of Tan sheep between the birth period and the Er-mao period were identified, among which 168 were upregulated and 196 were downregulated. Interestingly, the FOS proto-oncogene (FOS) (fold change = 22.67, P value = 2.15*10^-44) was the most significantly differentially expressed gene. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the FOS gene was significantly enriched in the signaling pathway related to hair follicle development. Immunohistochemical analysis showed that the FOS gene was expressed in the skin of Chinese Tan sheep at the birth and Er-mao periods, with significantly higher expression in the Er-mao period. Our findings suggest that the FOS gene promotes hair follicle development in Tan sheep.

Association Between the Lipid Profile and Renal Dysfunction in the Heart Failure Patients.

BACKGROUND/AIMS: In heart failure patients with high prevalence of chronic renal disease (CKD), hospitalization and mortality, whether the lipid profile was associated with renal dysfunction remained unknown. The present study intended to clarify the association between the lipid profile and renal dysfunction in the heart failure patients. METHODS: 336 hospitalized heart failure patients with left ventricle ejection fraction (LVEF) ≤45% and New York Heart Association (NYHA) class II-IV were enrolled. The estimated glomerular filtration rate (eGFR) < 90 mL/min·1.73 m2 was defined as renal dysfunction. The demographic, clinical data, blood samples and echocardiography were documented. The Pearson simple linear correlation was performed to evaluate the confounding factors correlated with eGFR. The significantly correlated factors were enrolled in Logistic regression as confounding factors to determine the association between the lipid profile and renal dysfunction in the heart failure patients. RESULTS: 182 patients (54.2%) had renal dysfunction and 154 patients (45.8%) did not have renal dysfunction. The waist circumference, platelet counts, platelet distribution width (PDW), high density lipoprotein-cholesterol (HDL-C), apolipoprotein A1 (apoA1), albumin and left ventricular ejection fraction (LVEF) are positively correlated with eGFR (all P< 0.05). Meanwhile, the age, mean platelet volume (MPV), neutrophilic granulocyte percentage (NEUT%), urea nitrogen (BUN), creatinine and total bilirubin (TBIL) are negatively correlated with eGFR (all P< 0.05). The total cholesterol (TC), triglyceride, low density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) show no correlation with eGFR. After the adjustment of sex, hypertension, diabetes mellitus, age, waist circumference, platelet counts, MPV, PDW, NEUT%, TBIL, albumin and LVEF, HDL-C is the only lipid factor still significantly associated with renal dysfunction in hospitalized heart failure patients (OR=0.119, P=0.003). CONCLUSION: Among the lipid profile of TC, triglyceride, LDL-C, HDL-C, apo A1 and apo B, the HDL-C is the only lipid factor significantly associated with renal dysfunction in hospitalized heart failure patients.

Extreme Right Axis Deviation in Acute Myocardial Infarction: A Hazardous Signal of Poor Prognosis.

BACKGROUND New-onset extreme right axis deviation and right bundle branch block (RBBB) are rare during acute myocardial infarction (AMI), and has only been reported in several cases reflecting the severity of AMI. It could predict severe clinical complications and higher risks in coronary artery disease. Although there is little electrophysiological explanation, the complications are severe. They should be emphasized in newly diagnosed extreme right axis deviation and RBBB in AMI. CASE REPORT A 72-year-old male was admitted to our department with a chief complaint of intermittent retrosternal chest pain and was diagnosed with extensive anterior myocardial infarction with RBBB, by elevated myocardial enzymes and ECG. The main wave direction of QRS in lead aVR was positive and showed an extreme right axis deviation. After a month, the patient's chest distress and the RBBB vanished, but a right axis deviation still existed. The echocardiogram showed prior extensive anterior myocardial infarction (including apex myocardia) and lower LVEF. CONCLUSIONS New diagnosed RBBB and right axis deviation is uncommon and could be a useful clue to evaluate myocardial ischemia in AMI cases. This electrocardiographic marker can identify coronary artery occlusion where ST-segments are hard to evaluate, and hence, patients may benefit most from early and complete revascularization strategies such as primary angioplasty.

G-T haplotype established by rs3785889-rs16941382 in GOSR2 gene is associated with coronary artery disease in Chinese Han population.

OBJECTIVES: The aim of the present study is to assess the association between the human GOSR2 gene and coronary artery disease using a haplotype-based case-control study in Chinese Han population. METHODS: A total of 283 coronary artery disease patients and 280 controls were genotyped for the human GOSR2 gene (rs197932, rs3785889, rs197922, rs17608766, and rs16941382). Data were analyzed for three separate groups: the total subjects, men, and women. RESULTS: For the total subjects, the frequency of the G-T haplotype established by rs3785889-rs16941382 was significantly higher in the coronary artery disease patients as compared to the control subjects (P=0.009). Multiple logistic regression analysis also confirmed that the subjects with G-T haplotype established by rs3785889-rs16941382 (homozygote) were found having significantly higher chance suffering from coronary artery disease than the ones without this haplotype (OR=1.887, P=0.007). CONCLUSIONS: The G-T haplotype established by rs3785889-rs16941382 may be a risk genetic marker for coronary artery disease patients in Chinese Han population.

Hamilton rating scale for depression-24 (HAM-D24) as a novel predictor for diabetic microvascular complications in type 2 diabetes mellitus patients.

The study was designed to investigate whether the hamilton rating scale for depression (24-items) (HAM-D24) can be used to predict the diabetic microvascular complications in type 2 diabetes mellitus (T2DM) patients. 288 hospitalized patients with T2DM were enrolled. Their diabetic microvascular complications including diabetic nephropathy, diabetic retinopathy, diabetic peripheral neuropathy and diabetic foot as well as demographic, clinical data, blood samples and echocardiography were documented. All the enrolled patients received HAM-D24 evaluation. The HAM-D24 score and incidence of depression in T2DM patients with each diabetic microvascular complication were significantly higher than those in T2DM patients without each diabetic microvascular complication. After the adjustment of use of insulin and hypoglycemic drug, duration of T2DM, mean platelet volume, creatinine, albumin, fasting glucose, glycosylated hemoglobin type A1C, left ventricular ejection fraction, respectively, HAM-D24 score was still significantly associated with diabetic microvascular complications (OR = 1.188-1.281, all P < 0.001). The AUC of HAM-D24 score for the prediction of diabetic microvascular complication was 0.832 (0.761-0.902). 15 points of HAM-D24 score was considered as the optimal cutoff with the sensitivity of 0.778 and specificity of 0.785. In summary, HAM-D24 score may be used as a novel predictor of diabetic microvascular complications in T2DM patients.

Association between neutrophilic granulocyte percentage and depression in hospitalized patients with heart failure.

BACKGROUND: Previous researches reveal that depression is associated with increased inflammatory markers. As a simple and cheap inflammatory marker, we hypothesize that neutrophilic granulocyte percentage is associated with depression in hospitalized heart failure patients, whose prevalence of depression is at a very high level. METHODS: Three hundred sixty-six cases of hospitalized heart failure patients with left ventricular ejection fraction (LVEF) ≤45% and New York Heart Association (NYHA) class II-IV were enrolled. All the enrolled patients received Hamilton Rating Scale for Depression (24-items) (HAM-D24). The demographic, clinical data, blood samples and echocardiography were documented. The Pearson simple linear correlation was performed to evaluate the confounding factors correlated with HAM-D24 depression index. The significantly correlated factors were enrolled as independent variables in Logistic regression to determine the risk or protective factors for depression, which was taken as dependent variable. RESULTS: Two hundred ten cases of hospitalized heart failure patients (57.4%) had depression. Among them, 134 patients (63.8%) had mild depression, 58 patients (27.6%) had moderate depression and 18 patients (8.6%) had severe depression. Pearson simple linear correlation revealed that in hospitalized patients with heart failure, the neutrophils granulocyte percentage was positively correlated with the HAM-D24 depression index (r = .435, p < .001). After the adjustment of age, BMI, number of members of the household, smoking index, New York Heart Association (NYHA) classification, hemoglobin, TC, LDL-C, creatinine, cystatin-C, TBIL and albumin, the neutrophils granulocyte percentage is still significantly associated with depression in hospitalized heart failure patients (OR = 1.046, p < .001). CONCLUSIONS: The neutrophils granulocyte percentage may be used as a new marker for depression in hospitalized heart failure patients.

Effects of Salt Loading on Plasma Osteoprotegerin Levels and Protective Role of Potassium Supplement in Normotensive Subjects.

BACKGROUND: Excess dietary salt is strongly correlated with cardiovascular disease, morbidity, and mortality. Conversely, potassium likely elicits favorable effects on cardiovascular disorders. In epidemiological studies, increased plasma osteoprotegerin (OPG) concentrations are associated with atherosclerosis and vascular deaths. Our study was designed to examine the effects of salt intake and potassium supplementation on plasma OPG levels in normotensive subjects.Methods and Results:The 18 normotensive subjects were selected from a rural community in China. They were sequentially maintained on low-salt diet for 7 days (3 g/day, NaCl), high-salt diet for 7 days (18 g/day), and high-salt diet with potassium supplementation for 7 days (18 g/day of NaCl+4.5 g/day of KCl). High-salt intake enhanced plasma OPG levels (252.7±13.9 vs. 293.4±16.1 pg/mL). This phenomenon was abolished through potassium supplementation (293.4±16.1 vs. 235.1±11.3 pg/mL). Further analyses revealed that the OPG concentration positively correlated with 24-h urinary sodium excretion (r=0.497, P<0.01). By contrast, OPG concentration negatively correlated with 24-h urinary potassium excretion (r=0.594, P<0.01). CONCLUSIONS: Salt loading can enhance the production of circulating OPG. Potassium supplementation can reverse the effects of excessive OPG. Our study results may improve our understanding of the roles of salt and potassium in the risk of cardiovascular disorders.

Elevation of Fasting Ghrelin in Healthy Human Subjects Consuming a High-Salt Diet: A Novel Mechanism of Obesity?

Overweight/obesity is a chronic disease that carries an increased risk of hypertension, diabetes mellitus, and premature death. Several epidemiological studies have demonstrated a clear relationship between salt intake and obesity, but the pathophysiologic mechanisms remain unknown. We hypothesized that ghrelin, which regulates appetite, food intake, and fat deposition, becomes elevated when one consumes a high-salt diet, contributing to the progression of obesity. We, therefore, investigated fasting ghrelin concentrations during a high-salt diet. Thirty-eight non-obese and normotensive subjects (aged 25 to 50 years) were selected from a rural community in Northern China. They were sequentially maintained on a normal diet for three days at baseline, a low-salt diet for seven days (3 g/day, NaCl), then a high-salt diet for seven days (18 g/day). The concentration of plasma ghrelin was measured using an immunoenzyme method (ELISA). High-salt intake significantly increased fasting ghrelin levels, which were higher during the high-salt diet (320.7 ± 30.6 pg/mL) than during the low-salt diet (172.9 ± 8.9 pg/mL). The comparison of ghrelin levels between the different salt diets was statistically-significantly different (p < 0.01). A positive correlation between 24-h urinary sodium excretion and fasting ghrelin levels was demonstrated. Our data indicate that a high-salt diet elevates fasting ghrelin in healthy human subjects, which may be a novel underlying mechanism of obesity.

Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway.

AIM: Matrine is an alkaloid from Sophora alopecuroides L, which has shown a variety of pharmacological activities and potential therapeutic value in cardiovascular diseases. In this study we examined the protective effects of matrine against diabetic cardiomyopathy (DCM) in rats. METHODS: Male SD rats were injected with streptozotocin (STZ) to induce DCM. One group of DCM rats was pretreated with matrine (200 mg·kg(-1)·d(-1), po) for 10 consecutive days before STZ injection. Left ventricular function was evaluated using invasive hemodynamic examination, and myocardiac apoptosis was assessed. Primary rat myocytes were used for in vitro experiments. Intracellular ROS generation, MDA content and GPx activity were determined. Real-time PCR and Western blotting were performed to detect the expression of relevant mRNAs and proteins. RESULTS: DCM rats exhibited abnormally elevated non-fasting blood glucose levels at 4 weeks after STZ injection, and LV function impairment at 16 weeks. The cardiac tissues of DCM rats showed markedly increased apoptosis, excessive ROS production, and activation of TLR-4/MyD-88/caspase-8/caspase-3 signaling. Pretreatment with matrine significantly decreased non-fasting blood glucose levels and improved LV function in DCM rats, which were associated with reducing apoptosis and ROS production, and suppressing TLR-4/MyD-88/caspase-8/caspase-3 signaling in cardiac tissues. Incubation in a high-glucose medium induced oxidative stress and activation of TLR-4/MyD-88 signaling in cultured myocytes in vitro, which were significantly attenuated by pretreatment with N-acetylcysteine. CONCLUSION: Excessive ROS production in DCM activates the TLR-4/MyD-88 signaling, resulting in cardiomyocyte apoptosis, whereas pretreatment with matrine improves cardiac function via suppressing ROS/TLR-4 signaling pathway.

Zirconium oxide ceramic foam: a promising supporting biomaterial for massive production of glial cell line-derived neurotrophic factor.

This study investigated the potential application of a zirconium oxide (ZrO2) ceramic foam culturing system to the production of glial cell line-derived neurotrophic factor (GDNF). Three sets of ZrO2 ceramic foams with different pore densities of 10, 20, and 30 pores per linear inch (PPI) were prepared to support a 3D culturing system. After primary astrocytes were cultured in these systems, production yields of GDNF were evaluated. The biomaterial biocompatibility, cell proliferation and activation of cellular signaling pathways in GDNF synthesis and secretion in the culturing systems were also assessed and compared with a conventional culturing system. In this study, we found that the ZrO2 ceramic foam culturing system was biocompatible, using which the GDNF yields were elevated and sustained by stimulated cell proliferation and activation of signaling pathways in astrocytes cultured in the system. In conclusion, the ZrO2 ceramic foam is promising for the development of a GDNF mass production device for Parkinson's disease treatment.

Prevention of pericardial constriction by transcatheter intrapericardial fibrinolysis with urokinase.

OBJECTIVE: To investigate whether intrapericardial urokinase irrigation along with pericardiocentesis could prevent pericardial constriction in patients with infectious exudative pericarditis. METHODS: A total of 94 patients diagnosed as infectious exudative pericarditis (34 patients with purulent pericarditis and 60 with tuberculous pericarditis, the disease courses of all patients were less than 1 month), 44 males and 50 females, aged from 9 to 66 years (mean 45.4 +/- 14.7 years), were consecutively recruited from 1993 to 2002. All individuals were randomly given either intrapericardial urokinase along with conventional treatment in study group, or conventional treatment alone (including pericardiocentesis and drainage) in control group. The dosage of urokinase ranged from 200000 to 600000 U (mean 320000 +/- 70000 U). The immediate effects were detected by pericardiography with sterilized air and diatrizoate meglumine as contrast media. The long-term investigation depended on the telephonic survey and echocardiographic examination. The duration of following-up ranged from 8 to 120 months (mean 56.8 +/- 29.0 months). RESULTS: Percutaneous intrapericardial urokinase irrigation promoted complete drainage of pericardial effusion, significantly reduced the thickness of pericardium (from 3.1 +/- 1.6 mm to 1.6 +/- 1.0 mm in study group, P < 0.001; from 3.4 +/- 1.6 mm to 3.2 +/- 1.8 mm in control group, P > 0.05, respectively), and alleviated the adhesion. Intrapericardial bleeding related to fibrinolysis was found in 6 of 47 patients with non-blood pericardial effusion and no systemic bleeding and severe puncture-related complication was observed. In follow-up, there was no cardiac death, and pericardial constriction events were observed in 9 (19.1%) of study group and 27 (57.4%) of control group. Cox analysis illustrated that urokinase could significantly reduce the occurrence of pericardial constriction (relative hazard coefficient = 0.185, P < 0.0001). CONCLUSION: The early employment of intrapericardial fibrinolysis with urokinase and pericardiocentesis appears to be safe and effective in preventing the development of pericardial constriction in patients with infectious exudative pericarditis.

[Effects of Evan Blue on perfused dimension display and rabbit left ventricular action potential].

OBJECTIVE: Simultaneous recording of transmembrane action potential at endocardium, midcardium and epicardium and transmural ECG in arterially perfused left ventricular preparation is a new method for researching into the mechanism about ventricular arrhythmia, and in this connection, how to distinguish the perfused area plays a key role in keeping preparations under normal condition. This study is aimed to evaluate the effects of Evan Blue on the displaying of the perfused area and on the characters of transmembrane action potential of the arterially perfused left ventricular preparations. METHODS: Rabbit left ventricular wedge preparations were perfused with Tyrode solution continuously via left circumflex, and the action potential of endocardium, midmyocardium, epicardium or transmural electrocardiogram were recorded simultaneously. The action poatential duration (APD), transmural dispersion of repolarization (TDR) or QT intervals were compared and the color variation of the preparations were studied before and 30 min after perfusion with Evan Blue. RESULTS: Under the basic stimulatory cycle length of 1000, 2000, 4000 ms, there was no significant difference of APD in the same transmural layer or TDR before and after Evan Blue perfusion (P<0.01), but APD or TDR stimulated at basic cycle length of 1000-4000 ms were all higher than those recorded at 500 ms (P<0.01); APDs of endocardium were much longer than those of epicardium or midmyocardium (P<0.01); there was no significant difference in APD, TDR and QT intervals before and after Evan Blue perfusion (P>0.05). No premature ventricular contractions and ventricular tachycardia happened during the experiments. CONCLUSION: Evan Blue can be used as a marker to identify the perfused area.

[Heterogeneity of Na+/Ca2+ exchanger current across the left ventricular wall of rabbit].

OBJECTIVE: To investigate the distribution characteristics of Na+/Ca2+ exchanger current (I(Na+/Ca2+)) across the left ventricular wall of rabbit and the relationship between I(Na+/Ca2+) and transmural depolarization heterogeneity. METHODS: By using whole-cell patch clamp techniques, action potentials (AP), I(Na+/Ca2+), and both rapid and slow components of delayed rectifier potassium current (I(Kr) and I(Ka)) were recorded in subendocardial (Endo), midmyocardial (M), and subepicardial (Epi) cells of the left ventricular wall of rabbit. RESULTS: AP duration in M cells was longer than that in Epi cells, P<0.01. At the test potential of +40 mV, outward I(Na+/Ca2+) in M cells was larger than that in Epi and Endo cells, P<0.01, P<0.05, respectively. At the test potential of -100 mV, inward I(Na+/Ca2+) in M cells was larger than that in Epi cells, P<0.05. At the test potential of +50 mV, the tail current density of I(Ka) in M cells was smaller than that in Epi cells, P<0.05, and there was no significant difference among the tail current densities of I(Kr) in Endo, M, and Epi cells. CONCLUSION: The distribution of I(Na+/Ca2+) and I(Ka) across the left ventricular wall of rabbit is unequal, which contributes to the transmural depolarization heterogeneity.

Adrenergic receptor antagonist prevents the left ventricle with chronic pressure-overload from electrical remodeling.

Experiments were performed to investigate the effects of long-term treatment with adrenergic receptor antagonist on electrical remodeling of the left ventricle with chronic pressure-overload. New Zealand rabbits underwent subtotal banding of superrenal abdominal aorta. At 10 weeks after surgery, echocardiography examination was performed, then action potential (AP), inward rectifier potassium current (I(Ki)), delayed rectifier potassium current (I(K)) and Na(+)/Ca(2+) exchanger current (I(Na(+)/Ca(2+))) were recorded in midmyocardial cells isolated from left ventricle of abdominal aorta banded group (banded group), abdominal aorta banding plus Carvedilol intervention group (Carvedilol group), and normal control group rabbits by using the whole-cell patch-clamp techniques. The results showed that left ventricular mass index in control, banded, and Carvedilol groups were 1.78+/-0.06 (n=7), 2.33+/-0.11 (n=7), and 1.87+/-0.08 (n=7), respectively (banded vs control and Carvedilol, P<0.01). At basic cycle length of 2 s, AP duration (measured at 90% repolarization, APD(90), ms) in control, banded, and Carvedilol groups were 522.0+/-19.5 (n=6), 664.7+/-46.2 (n=7), 567.8+/-14.3 (n=8) respectively (banded vs control, P<0.01; Carvedilol vs banded, P<0.05). At test potential of -100 mV, inward I(Ki) density (pA/pF) in control, banded, and Carvedilol groups were -11.8+/-0.50 (n=8), -8.07+/-0.28 (n=8), -10.69+/-0.35 (n=8) respectively (banded vs control and Carvedilol, P<0.01). At test potential of +50 mV, I(K) tail current density (pA/pF) in control, banded, and Carvedilol groups were 0.59+/-0.04 (n=8), 0.40+/-0.02 (n=9), 0.51+/-0.02 (n=8) respectively (banded vs control, P<0.01; Carvedilol vs banded, P<0.05). At test potential of +60 mV, outward I(Na(+)/Ca(2+)) density (pA/pF) in control, banded, and Carvedilol groups were 1.06+/-0.11 (n=8), 1.54+/-0.10 (n=9), 1.24+/-0.07 (n=8), respectively (banded vs control and Carvedilol, P<0.01). At test potential of -120 mV, inward I(Na(+)/Ca(2+)) density (pA/pF) in control, banded, and Carvedilol groups were -0.54+/-0.06 (n =8), -0.75+/-0.04 (n=9), -0.60+/-0.03 (n=8), respectively (banded vs control, P<0.01; Carvedilol vs banded, P<0.05). It is shown that long-term treatment with Carvedilol not only prevents development of cardiac hypertrophy, but also improves the electrophysiological alterations in rabbit hearts with chronic pressure-overload. This finding may add new electrophysiological evidence for the treatment of heart failure and hypertension with adrenergic receptor antagonist.

[Na+/Ca2+ exchanger current and K+ current remodeling in midmyocardial cells of hypertrophic left ventricle].

OBJECTIVE: To investigate the characteristics of Na+/Ca2+ exchanger current (INa+ /Ca2+) and K+ current remodeling in midmyocardial cells of hypertrophic left ventricle for understanding the ionic basis of arrhythmia of the hypertrophic heart. METHODS: Twenty New Zealand rabbits were divided equally into normal control group and operation group, and in the latter, left ventricular hypertrophy was induced in the rabbits by partial ligation of the abdominal aorta. Action potentials, INa+/Ca2+, slowly activating delayed rectifier K+ current (IKs) and rapidly activating delayed rectifier K+ current (IKr) were recorded in the two groups by using whole-cell patch-clamp technique. RESULTS: At the basic cycle length of 2 s, 90% action potential duration (APD90) in control and operation groups was 522.0+/-19.5 ms (n=6) and 664.7+/-32.7 ms (n=7) respectively; at the testing potential of +40 mV, outward INa+/Ca2+ density in the two groups was 0.94+/-0.11 pA/pF (n=9) and 1.30+/-0.11 pA/pF (n=8) respectively; the testing potential of -100 mV elicited inward INa+/Ca2+ density of 0.40+/-0.05 pA/pF (n=9) and 0.56+/-0.02 pA/pF (n=8) respectively. The testing potential of +50 mV induced IKs tail current density of 0.26+/-0.03 pA/pF (n=8) and 0.17+/-0.01 pA/pF (n=9), and IKr tail current density of 0.34+/-0.02 pA/pF (n=8) and 0.23+/-0.02 pA/pF (n=9) respectively. Statistically significant differences were identified between the control and operation groups in all the above indices measured. CONCLUSION: The characteristics of electrical remodeling changes in midmyocardial cells of hypertrophic left ventricle, exhibited by prolonged action potential, up-regulated INa+/Ca2+ and down-regulated IKs and IKr.

Curcumin ameliorates left ventricular function in rabbits with pressure overload: inhibition of the remodeling of the left ventricular collagen network associated with suppression of myocardial tumor necrosis factor-alpha and matrix metalloproteinase-2 expression.

OBJECTIVE: Curcumin is a wide-spectrum cellular protector with antiinflammatory, antioxidizant, and antifibrotic effects. This study was conducted to investigate its effects on myocardial collagen remodeling in pressure overloaded rabbits. METHODS AND RESULTS: Pressure overloaded rabbits were established by partial abdominal aorta ligation. The rabbits were divided into the sham-operation group, vehicle group and curcumin group. Curcumin was administered orally at a dose of 100 mg/kg.d in 10 ml of 2.5% polyethylene glycol solution and the other 2 groups were given the same dose of polyethylene glycol solution. Compared with the vehicle group, left ventricular function in the curcumin group was significantly ameliorated, as indicated by decreased left ventricular end-diastolic pressure, left ventricle weight to body weight ratio, and the left ventricular posterior wall thickness. The collagen volume fraction in the curcumin group was also reduced. Myocardial tumor necrosis factor (TNF)-alpha and matrix metalloproteinase (MMP)-2 expression were significantly overexpressed in the vehicle group and markedly suppressed in the curcumin group at both the 4th and 8th weeks. At the end of the 8th week, the ejection fraction in the curcumin group was increased compared with that in the vehicle group. CONCLUSION: Curcumin improved left ventricular function in pressure overloaded rabbits. This might be due to inhibition of collagen remodeling associated with suppression of myocardial expression of tumor necrosis factor-alpha, and matrix metalloproteinase-2.

[Effect of xuezhikang on blood lipids, serum oxidized low density lipoprotein, C-reactive protein and fibrinogen in patients with unstable angina pectoris].

OBJECTIVE: To study the lipid regulatory effect of Xuezhikang (XZK) and its effects on serum oxidized low density lipoprotein (OX-LDL), C-reactive protein (CRP) and fibrinogen (FIB) in patients with unstable angina pectoris (UAP). METHODS: UAP patients with hyperlipidemia were treated with XZK 0.6 g, orally taken, twice a day for 2 successive months followed by half dosage for 2 months. To UAP patients with normal blood lipids, Vit E was given orally for 4 months. Levels of blood lipids, OX-LDL, CRP, FIB at the time of entry, 1st and 2nd month of the therapeutic course were observed and end-point events in the two groups was compared. RESULTS: XZK can reduce the serum level of total cholesterol, low density lipoprotein after being administered for 1 month, and the effect further elevated after 2 months. Its effect in lowering triglycerides and increasing high density lipoprotein initiated after 2 months administration. Compared with effect of Vit E, XZK can significantly lower the serum OX-LDL, CRP and FIB after 2 months administration, and reduce the end-point events in 4 months. CONCLUSION: XZK has good regulatory effect on blood lipids, it also can inhibit the development of inflammation in coronary plaque, therefore, is beneficial to the prognosis of UAP patients.