The role of acute heart failure index (AHFI) combined with emergency heart failure mortality risk grade (EHMRG) in the evaluation of clinical outcomes and prognosis in patients with acute heart failure.

OBJECTIVE: To investigate clinical value for the risk model of acute heart failure index (AHFI) combined with emergency heart failure mortality risk grade (EHMRG) in evaluating clinical outcomes and prognosis of patients with acute heart failure (AHF). METHODS: The present prospective observational cohort study enrolled a total of 228 patients with AHF who were admitted to our hospital from January 2019 to January 2020. The AHF patients were divided into four groups: (1) the high AHFI and high EHMRG group, n = 61; (2) the low AHFI and low EHMRG group, n = 92; (3) the high AHFI and low EHMRG group, n = 34; (4) the low AHFI and high EHMRG group, n = 41. AHFI and EHMRG were used to identify the risk of death for AHF patients. Serum levels of Troponin I, B-type natriuretic peptide (BNP), and NT-pro-B-type natriuretic peptide (NT-proBNP) were detected by the ELISA method. Kaplan-Meier curve was performed for analysis of survival time and a logistic regression model was used to analyse 1-year mortality of patients. Pearson's analysis was used to determine the correlation between biomarkers and EHMRG. RESULTS: AHFI combined with the EHMRG model was associated with cardiac function status and EHMRG score was positively related to the level of Troponin I, BNP, and NT-proBNP. AHF high-risk AHFI and high-risk EHMRG indicated that patients might have a higher incidence of MACEs during hospitalisation. In addition, AHFI and high-risk EHMRG groups had shorter survival times, and AHFI was associated with 1-year mortality and was the risk factor for 1-year mortality. CONCLUSION: AHFI combined with a high EHMRG risk model was associated with clinical outcomes and prognosis.

Desmin Correlated with Cx43 May Facilitate Intercellular Electrical Coupling during Chronic Heart Failure.

Desmin is one of five major intermediate filament proteins in cardiomyocytes. Desmin contributes to the maintenance of healthy muscle. The desmin content in cardiomyocytes directly affects the long-term prognosis of patients with heart failure, and lack of desmin leads to myocyte contractile dysfunction. However, the mechanism is elusive. In this study, we measured desmin expression using western blotting and qPCR in the failed hearts of human patients and rats. Our results showed that desmin content was reduced at the protein level in failed hearts and isolated cardiomyocytes. The association of desmin and the gap junction proteins connexin 43 (Cx43) and zonula occludens-1 (ZO-1) was also investigated. Immunoprecipitation assay showed that desmin was associated with Cx43 in cardiomyocytes. To compare the electrical integration of skeletal myoblasts in cocultures with cardiac myocytes, familial amyloid polyneuropathy (FAP) activation rate was found in 33% desmin overexpressing skeletal myoblasts. Desmin not only affected Cx43 and ZO-1 expression but also facilitated the complex of Cx43 and ZO-1 in skeletal myoblasts, which enhanced cell-to-cell electrical coupling of skeletal myoblasts with cardiac myocytes. Desmin has potential as a novel therapeutic target for heart failure. Preservation of desmin may attenuate heart failure.

Artemisinin suppresses myocardial ischemia-reperfusion injury via NLRP3 inflammasome mechanism.

Artemisinin is known for its pharmaceutical effect against malaria and received increased attention for its other potential function. Mounting evidence suggest that artemisinin could also exert cardioprotective effects while the understanding of its regulatory mechanism is still limited. This study is designed to investigate the role of artemisinin in myocardial ischemia/reperfusion (I/R) injury and the involvement of NLRP3 inflammasome. Artemisinin was administrated for 14 consecutive days intragastrically before I/R injury. Cardiac function was assessed by echocardiography. Infarct area was observed through HE and TTC staining. Apoptosis and autophagy were assessed by TUNEL and Western blotting. The artemisinin-treated myocardial I/R rats demonstrated less severe myocardial I/R injury (smaller infarct size and lower CK-MB, LDH), significant inhibition of cardiac autophagy (decreased LC3II/I and increased p62), improved mitochondrial electron transport chain activity, concomitant with decreased activation of NLRP3 inflammasome (decreased NLRP3, ASC, cleaved caspase-1, IL-1ß). In conclusion, our findings further confirmed that activation of the NLRP3 inflammasome pathway is involved in myocardial I/R injury, whereas artemisinin preconditioning could effectively protect against myocardial I/R injury through suppression of NLRP3 inflammasome activation. Therefore, the NLRP3 inflammasome might serve as a promising therapeutic target providing new mechanisms for understanding the effect of artemisinin during the evolution of myocardial infarction.

Histone demethylase JARID1B regulates proliferation and migration of pulmonary arterial smooth muscle cells in mice with chronic hypoxia-induced pulmonary hypertension via nuclear factor-kappa B (NFkB).

Chronic hypoxia-induced pulmonary hypertension (PH) is a disorder that is characterized by increased pulmonary arterial pressure resulting from lung diseases or shortage of oxygen in the body. Excess proliferation of pulmonary vascular cells such as pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs) plays a critical role in the pathogenesis of PH. Recent evidence indicates that, in addition to genetic predisposition and environmental factors, epigenetic mechanisms play a pivotal role in etiology of PH. In this study, we investigated the possible role played by jumonji AT-rich interactive domain 1B (JARID1B), a histone demethylase, in regulating the proliferation of vascular smooth muscle cells in chronic hypoxia-induced PH condition. Quantitative polymerase chain reaction analysis of samples from rats with PH showed an elevated expression of JARID1B in their PASMCs, positively correlating with increased nuclear factor-kappa B (NFkB) expression. Further functional studies in vitro indicated that overexpression of JARID1B increased the proliferation and migration of PASMCs, which were inhibited by depletion of NFkB. Genomewide transcriptional analysis revealed that the JARID1B regulated NFkB signaling pathway by directly binding to its promoter. We have also shown that JARID1B indirectly regulates the expression of vascular endothelial growth factor via NFkB signaling and hence may also play a crucial role in controlling PAECs, leading to changes in vascular architecture in PH. Our findings could lead to further studies on the role of JARID1B in PH etiology and therefore could lead to a potential therapeutic target for chronic hypoxia induced pulmonary hypertension.

Sonodynamic Therapy Mediated by Emodin Induces the Oxidation of Microtubules to Facilitate the Sonodynamic Effect.

In previous studies, sonodynamic therapy mediated by emodin (emodin-SDT) induced cytoskeletal filament disruption and apoptosis of THP-1-derived macrophages. In this research, we investigated the underlying mechanism. THP-1-derived macrophages were incubated with emodin and exposed to ultrasound irradiation. After emodin-SDT, we measured the production of reactive oxygen species (ROS) and analyzed the level of amino acid oxidation in microtubules, the cleavage of microtubules and the mitochondrial membrane potential (MMP). We found that intracellular emodin accumulated mainly on microtubules. After emodin-SDT, generation of ROS was evident. Analysis of the carbonyl content of proteins suggested oxidation of microtubules. Microtubules were disrupted after emodin-SDT, and the antioxidant N-acetyl-L-cysteine prevented this disruption. MMP decreased after emodin-SDT, and this effect could be prevented by N-acetyl-L-cysteine. We conclude that emodin-SDT induces the generation of ROS. The oxidation of microtubules leads to its cleavage and the subsequent decline in MMP.

MiR-130a inhibition protects rat cardiac myocytes from hypoxia-triggered apoptosis by targeting Smad4.

BACKGROUND: Cardiomyocyte death facilitates the pathological process underlying ischaemic heart diseases, such as myocardial infarction. Emerging evidence suggests that microRNAs play a critical role in the pathological process underlying myocardial infarction by regulating cardiomyocyte apoptosis. However, the relevance of miR-130a in regulating cardiomyocyte apoptosis and the underlying mechanism are still uncertain. AIM: We sought to explore the regulatory effect of miR-130a on hypoxic cardiomyocyte apoptosis. METHODS: The expression of miR-130a was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell survival was determined by the MTT assay. The lactate dehydrogenase (LDH) assay was performed to deter-mine the severity of hypoxia-induced cell injury. Apoptosis was assessed via caspase-3 analysis. Protein expression level was determined by Western blotting. The genes targeted by miR-130a were predicted using bioinformatics and were validated via the dual-luciferase reporter assay system. RESULTS: We found that miR-130a expression was greatly increased in hypoxic cardiac myocytes, and that the downregulation of miR-130a effectively shielded cardiac myocytes from hypoxia-triggered apoptosis. In bioinformatic analysis the Smad4 gene was predicted to be the target of miR-130a. This finding was validated through the Western blot assay, dual-luciferase reporter gene assay, and qRT-PCR. MiR-130a inhibition significantly promoted the activation of Smad4 in hypoxic cardiomyocytes. Inter-estingly, knockdown of Smad4 markedly reversed the protective effects induced by miR-130a inhibition. Moreover, we found that the inhibition of miR-130a promoted the activation of transforming growth factor-b1 signalling. Blocking of Smad4 signal-ling significantly abrogated the protective effects of miR-130a inhibition. CONCLUSIONS: The findings indicate that inhibition of miR-130a, which targets the Smad4 gene, shields cardiac myocytes from hypoxic apoptosis. This study offers a novel perspective on the molecular basis of hypoxia-induced cardiomyocyte apoptosis and suggests a possible drug target for the treatment of myocardial infarction.

5-Aminolevulinic Acid-Mediated Sonodynamic Therapy Inhibits RIPK1/RIPK3-Dependent Necroptosis in THP-1-Derived Foam Cells.

Necroptosis, or programmed necrosis, contributes to the formation of necrotic cores in atherosclerotic plaque in animal models. However, whether inhibition of necroptosis ameliorates atherosclerosis is largely unknown. In this study, we demonstrated that necroptosis occurred in clinical atherosclerotic samples, suggesting that it may also play an important role in human atherosclerosis. We established an in vitro necroptotic model in which necroptosis was induced in THP-1-derived foam cells by serum deprivation. With this model, we demonstrated that 5-aminolevulinic acid-mediated sonodynamic therapy (ALA-SDT) inhibited necroptosis while promoting apoptosis. ALA-SDT activated the caspase-3 and caspase-8 pathways in foam cells, which is responsible for the switch from necroptosis to apoptosis. The inhibition of either caspase-8 or caspase-3 abolished the anti-necroptotic effect of ALA-SDT. In addition, we found that caspase-3 activation peaked 4 hours after ALA-SDT treatment, 2 hours earlier than maximal caspase-8activation. Taken together, our data indicate that ALA-SDT mediates the switch from necroptosis to apoptosis by activating the caspase-3 and caspase-8 pathways and may improve the prognosis of atherosclerosis.

Streptomycin inhibits electrophysiological changes induced by stretching of chronically infarcted rat hearts.

OBJECTIVE: To investigate stretch-induced electrophysiological changes in chronically infarcted hearts and the effect of streptomycin (SM) on these changes in vivo. METHODS: Sixty Wistar rats were divided randomly into four groups: a control group (n=15), an SM group (n=15), a myocardial infarction (MI) group (n=15), and an MI+SM group (n=15). Chronic MI was obtained by ligating the left anterior descending branch (LAD) of rat hearts for eight weeks. The in vivo blockade of stretch-activated ion channels (SACs) was achieved by intramuscular injection of SM (180 mg/(kg∙d)) for seven days after operation. The hearts were stretched for 5 s by occlusion of the aortic arch. Suction electrodes were placed on the anterior wall of left ventricle to record the monophasic action potential (MAP). The effect of stretching was examined by assessing the 90% monophasic action potential duration (MAPD90), premature ventricular beats (PVBs), and ventricular tachycardia (VT). RESULTS: The MAPD90 decreased during stretching in both the control (from (50.27±5.61) ms to (46.27±4.51) ms, P<0.05) and MI groups (from (65.47±6.38) ms to (57.47±5.76 ms), P<0.01). SM inhibited the decrease in MAPD90 during inflation ((46.27±4.51) ms vs. (49.53±3.52) ms, P<0.05 in normal hearts; (57.47±5.76) ms vs. (61.87±5.33) ms, P<0.05 in MI hearts). The occurrence of PVBs and VT in the MI group increased compared with that in the control group (PVB: 7.93±1.66 vs. 1.80±0.86, P<0.01; VT: 7 vs. 1, P<0.05). SM decreased the occurrence of PVBs in both normal and MI hearts (0.93±0.59 vs. 1.80±0.86 in normal hearts, P<0.05; 5.40±1.18 vs. 7.93±1.66 in MI hearts, P<0.01). CONCLUSIONS: Stretch-induced MAPD90 changes and arrhythmias were observed in chronically infarcted myocardium. The use of SM in vivo decreased the incidence of PVBs but not of VT. This suggests that SACs may be involved in mechanoelectric feedback (MEF), but that there might be other mechanisms involved in causing VT in chronic MI.

Prioritizing disease candidate proteins in cardiomyopathy-specific protein-protein interaction networks based on "guilt by association" analysis.

The cardiomyopathies are a group of heart muscle diseases which can be inherited (familial). Identifying potential disease-related proteins is important to understand mechanisms of cardiomyopathies. Experimental identification of cardiomyophthies is costly and labour-intensive. In contrast, bioinformatics approach has a competitive advantage over experimental method. Based on "guilt by association" analysis, we prioritized candidate proteins involving in human cardiomyopathies. We first built weighted human cardiomyopathy-specific protein-protein interaction networks for three subtypes of cardiomyopathies using the known disease proteins from Online Mendelian Inheritance in Man as seeds. We then developed a method in prioritizing disease candidate proteins to rank candidate proteins in the network based on "guilt by association" analysis. It was found that most candidate proteins with high scores shared disease-related pathways with disease seed proteins. These top ranked candidate proteins were related with the corresponding disease subtypes, and were potential disease-related proteins. Cross-validation and comparison with other methods indicated that our approach could be used for the identification of potentially novel disease proteins, which may provide insights into cardiomyopathy-related mechanisms in a more comprehensive and integrated way.

The sonodynamic effect of curcumin on THP-1 cell-derived macrophages.

Curcumin is extracted from the rhizomes of the traditional Chinese herb Curcuma longa and has been proposed to function as a photosensitizer. The potential use of curcumin as a sonosensitizer for sonodynamic therapy (SDT) requires further exploration. This study investigated the sonodynamic effect of curcumin on macrophages, the pivotal inflammatory cells in atherosclerotic plaque. THP-1-derived macrophages were incubated with curcumin at a concentration of 40.7 µmol/L for 2 h and then exposed to pulse ultrasound irradiation (2 W/cm(2) with 0.86 MHz) for 5-15 min. Six hours later, cell viability was decreased in cells that had been treated with ultrasound for 10 and 15 min. After ultrasound irradiation for 15 min, the ratio of apoptotic and necrotic cells in SDT group was higher than that in ultrasound group, and the ratio of apoptotic cells was higher than that of necrotic cells. Both loss of mitochondrial membrane potential and morphological changes of cytoskeleton were apparent 2 h after treatment with curcumin SDT. These findings support that curcumin had sonodynamic effect on THP-1-derived macrophages and that curcumin SDT could be a promising treatment for atherosclerosis.

Sonodynamic effect of an anti-inflammatory agent--emodin on macrophages.

Emodin has been used as an anti-inflammatory agent and inflammation is a crucial feature of atherosclerosis. Here, we investigated the sonodynamic effect of emodin on macrophages, the pivotal inflammatory cells in atherosclerotic plaque. THP-1 derived macrophages were cultured with emodin and exposed to ultrasound. Six hours later, unlike the cells treated for 5 and 10 min, the viability of cells treated for 15 min decreased significantly and the cells showed typical apoptotic chromatin fragmentation. The percentage of apoptotic and necrotic cells in the sonodynamic therapy (SDT) group was higher than that in the ultrasound group. Two hours after treatment for 15 min, the cytoskeleton lost its original features as the filaments dispersed and the cytoskeletal proteins aggregated. The percentage of cells with disturbed cytoskeletal filaments in the SDT group was higher than that in the ultrasound group. These results suggest emodin has a sonodynamic effect on macrophages and might be used as a novel sonosensitizer for SDT for atherosclerosis.

Regional differential expression of TREK-1 at left ventricle in myocardial infarction.

BACKGROUND: Altered membrane electrophysiology contributes to arrhythmias after myocardial infarction (MI). TREK-1 channel is essential in various physiological and pathological conditions through its regulation on resting membrane potential and voltage-dependent action potential duration. OBJECTIVES: The aim of this study was to investigate changes in gene expression and electrophysiology of TREK-1 in the left ventricle in a MI model. METHODS: Fifty-five rats were divided into 5 groups: sham-operated group, 6 hours, 24 hours, 3 days, and 7 days post MI group (n=11 per group). TREK-1 messenger RNA (mRNA) expression level in the infarct region (IR) and infarct border region (IBR) were quantified by real-time polymerase chain reaction (PCR), and TREK-1 current density at the IBR was recorded with whole-cell patch-clamp technique. RESULTS: TREK-1 mRNA expression decreased significantly in both endocardial and epicardial cells in the infarct region after MI. Conversely, TREK-1 increased significantly in endocardial and epicardial cells from the IBR (P<0.01). Current density of TREK-1 at IBR increased significantly in both epicardial and endocardial cells after MI (P<0.01). CONCLUSIONS: TREK-1 demonstrates specific changes in expression and electrophysiological function in left ventricle post MI. These results suggest that TREK-1 may participate in pathophysiologic alteration and electrical remodelling of left ventricular myocardium after MI, which may eventually lead to post-MI ventricular arrhythmias.

Berberine cooperates with adrenal androgen dehydroepiandrosterone sulfate to attenuate PDGF-induced proliferation of vascular smooth muscle cell A7r5 through Skp2 signaling pathway.

Platelet-derived growth factor (PDGF) is released from vascular smooth muscle cell (VSMC), after percutaneous coronary intervention and is related with neointimal proliferation and restenosis. Adrenal steroid dehydroepiandrosterone sulfate (DHEAS), the sulfated prohormone of dehydroepiandrosterone has shown remarkable biological activity against proliferation of VSMC in some animal and clinical studies. Combinations of DHEAS with other agents have also shown promising results, with acquiring more efficient effect. Berberine is a naturally occurring isoquinoline alkaloid. To investigate their effects in combination, a VSMC cell line A7r5 was stimulated by PDGF-BB (dimer of the B chain of PDGF), and then treated with berberine and/or DHEAS in the current study. Cell proliferation assay, cell cycle assay, Western blot, and co-immunoprecipitation were analyzed in A7r5 cells. Antiproliferative effects of berberine and/or DHEAS targeting the Skp2/p27 pathways were evaluated. Berberine and DHEAS can both inhibit the growth of A7r5 cells. Berberine induces cell cycle arrest and potentiates the inhibitory effect of DHEAS through disrupting the binding of p27, p21 with Skp2. Berberine and DHEAS decreased the expression of CDK2, CDK4, PCNA, cyclin D1, and cyclin E, which was induced by PDGF-BB. Being treated with berberine and DHEAS also promoted p27 and p21 bind to CDK2, so the proliferation of A7r5 cells induced by PDGF-BB was inhibited. The data provide evidence that berberine acts through the inhibition of p27-Skp2 and p21-Skp2 with subsequent activation of the cell cycle arrest, which leads to the increase in sensitivity to DHEAS. In summary, the findings suggest that combined berberine and DHEAS will be active in the prevention of restenosis after angioplasty treatment, and the treatment of atherosclerosis.

Valsartan alleviates atherosclerotic lesions in pulmonary arteries of rabbits via an endothelium-dependent mechanism.

OBJECTIVE: Angiotensin II plays an important role in the pathogenesis of atherosclerosis. This study was designed to examine the effect of valsartan, an angiotensin receptor blocker, on atherosclerotic lesions in pulmonary arteries of rabbits with atherosclerosis induced by a high-cholesterol (HC) diet. METHODS: Male New Zealand rabbits were randomly divided into four groups: control, HC without valsartan, HC with 3 mg/kg/d valsartan, and HC with 10 mg/kg/d valsartan. Following 12 weeks of treatment, serum lipid profiles were determined. Pulmonary arteries were harvested and stained with Sudan IV for evaluation of atherosclerotic lesions. The middle lobes of the rabbit lungs were isolated, embedded in paraffin, and sectioned and stained with haematoxylin and eosin. Nitric oxide (NO) and endothelin-1 (ET-1) levels were determined in pulmonary arteries by nitrate reductase assay and radioimmunoassay, respectively. RESULTS: HC feeding altered serum lipid levels and induced atherosclerotic lesions in pulmonary arteries. Although 12 weeks of valsartan treatment failed to alter serum lipid levels, it significantly ameliorated HC-induced atherosclerotic lesions. Lesion areas, inflammatory cell infiltration, and occlusions of small arteries of lungs were reduced. Moreover, the endothelium-derived NO levels in pulmonary arteries were increased by valsartan treatment (10 mg/kg/d) compared to levels in the HC group. ET-1 levels were decreased by valsartan treatment compared to levels in the HC group. NO and ET-1 levels were not altered by valsartan at 3 mg/kg/d. CONCLUSION: Our data demonstrates that HC diet-induced atherosclerotic lesions in rabbit pulmonary arteries can be ameliorated by treatment with valsartan, possibly through a NO and ET-1-dependent mechanism.

Early use of omeprazole benefits patients with acute myocardial infarction.

BACKGROUND: Bleeding complications are not uncommon in patients with acute myocardial infarction (AMI) during treatments. How to prevent the occurrence of upper gastrointestinal bleeding in AMI patients has become one of the most intractable problems. And there are conflicting data on the efficacy and complication rate of omeprazole treatment. We conducted an intervention study to determine whether using omeprazole could benefit AMI patients. METHODS: A total of 237 patients with AMI were divided into two groups at random: omeprazole group including 114 patients and control group including 123 patients. Omeprazole 40 mg by intravenous drip was given to the patients in omeprazole group when they were admitted to the hospitals. From the second day they were given omeprazole 20 mg per day by oral administration for 7 days. In contrast, no gastric acid inhibitor was given to the patients in control group. The incidence of upper gastrointestinal bleeding, the recanalization rate and overall mortality in both groups were observed. RESULTS: The incidence of upper gastrointestinal bleeding in omeprazole group was 5.3% (6/114) which was much lower than 14.6% (18/123) in control group (P = 0.017), but the recanalization rate had no significant difference between the two groups (P = 0.681). The overall mortality in omeprazole group was lower than that of control group (3.5% vs. 10.6%, P = 0.035). CONCLUSIONS: Our findings suggest that early use of omeprazole in AMI patients could decrease the incidence of upper gastrointestinal bleeding and the overall mortality, without influencing the recanalization rate. Early use of omeprazole might benefit AMI patients.

Testosterone deprivation by castration impairs expression of voltage-dependent potassium channels in rat aorta.

In this study, we explored the effects of testosterone deprivation on the expression of voltage-dependent potassium (Kv) channels in vascular smooth muscle cells (VSMCs) in rats. Six months after mature male Wistar rats were castrated, functional and posttranscriptional alterations of voltage-dependent potassium channels were detected using isometric tension measurement, whole-cell patch-clamp and western blot analysis. Constriction of aortic artery rings in response to 4-aminopyridine was significantly decreased 6 months after castration. A significant decrease in the amplitude of voltage-dependent potassium currents of aortic artery smooth muscle cells was detected in castrated rats compared with control rats. The level of expression of Kv1.5 channel protein was decreased. The decreased function and suppressed Kv1.5 protein expression of Kv channels after castration were restored by testosterone replacement. We concluded that long-term deprivation of endogenous testosterone in rats significantly attenuated the function of voltage-dependent potassium channels, and that a decreased expression of Kv1.5 channel protein accounted for this alteration. Restoration of physiological concentrations of testosterone restored the impaired function of voltage-dependent potassium channels, which may provide evidence for the beneficial effects of clinical testosterone replacement.

Relationship between testosterone and indexes indicating endothelial function in male coronary heart disease patients.

AIM: To investigate the relationship between androgen level and the indexes indicating endothelial function in male patients with coronary heart disease (CHD). METHODS: We registered the following data for 106 50-70-year-old men: age, weight, blood lipid, including total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglyceride, whether a smoker, sugar levels, blood pressure, free testosterone (FT), vascular cell adhesion molecule-1 (VCAM-1) and the intima-media thickness (IMT) of common carotid artery, common carotid diameter, maximum velocity in systolic phase, minimum velocity in diastolic phase and resistant index. Among the 106 men, 51 were patients with CHD. The relationships between FT level, VCAM-1 concentration and IMT were examined, respectively, using a stepwise linear regression technique among all the 106 men. RESULTS: There was no statistical difference in terms of age, blood pressure, whether a smoker, sugar levels, HDL-C, minimum velocity in diastolic phase, resistant index between male CHD patients and controls; whereas results for weight, total cholesterol, low density lipoprotein cholesterol, triglyceride, VCAM-1 and IMT of male CHD patients were higher than those of controls; FT level and maximum velocity in systolic phase were lower. It was found that among all the objects, FT level was inversely correlated with IMT and VCAM-1 concentration. CONCLUSION: FT level was inversely correlated with VCAM-1 concentration and IMT which are indicators of endothelial function.

[The effect of homocysteine on fibrinolytic system in human umbilical vein endothelial cells].

OBJECTIVES: To investigate the relationship between homocysteine (Hcy) and the fibrinolytic system in acute myocardial infarction (AMI) and human umbilical vein endothelial cells (HUVEC). METHODS: Cultured HUVEC was divided into 10 groups (0, 10, 50, 200, 500 micromol/L Hcy with or without 15 micromol/L of folic acid). There were 53 patients of acute myocardial infarction (AMI) and 48 healthy controls. The plasminogen activator inhibitor-1 (PAI-1) and activator of plasminogen (tPA) antigen levels in HUVEC's supernatant and plasma were measured with Elisa kit. Concentration of plasma Hcy was measured by reverse-phase high-performance liquid chromatography with precolumn derivatization and fluorometric detection in the patients and healthy controls. Total RNA was extracted using the guanidinium isothiocyanate method. The semi-quantification of PAI-1 and tPA mRNA in HUVEC was carried out by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: (1) PAI-1 mRNA and secreted protein levels were both significantly enhanced by Hcy at the concentration of 500 micromol/L, compared with the control group (P < 0.05). (2) The tPA mRNA and antigen levels were decreased significantly at concentration of 500 micromol/L of Hcy, compared with that of 10 micromol/L Hcy (P < 0.05), but compared with the control group (0 micromol/L), the tPA mRNA and antigen levels of 10 micromol/L of Hcy were much higher (P < 0.05). (3) The addition of folic acid reduced PAI-1 but increased tPA at both mRNA and protein levels, which were both obvious at concentrations of 500 micromol/L Hcy, compared with only Hcy group (P < 0.05). (4) Hcy, tPA, and PAI-1 antigen levels were increased in AMI group. Hcy is a independent risk factor of AMI (P < 0.05). There weren't significant correlation between Hcy and tPA or Hcy and PAI-1 in both groups (P > 0.05), although the coefficient correlation was higher in patients than in controls. CONCLUSIONS: These results suggested that hyperhomo-cysteinemia increased the incidence of thrombotic disease, which may be caused by decreasing the activity of fibrinolytic system, whereas, folic acid may be protective against the toxic action of Hcy.

[Testosterone has beneficial effects on human umbilical vein endothelial cells].

AIM: To investigate the influences of testosterone with varied concentrations on the functions of HUVEC. METHODS: Human umbilical vein endothelial cells within 2-3 passages were cultured with testosterone (3 x 10(-10) to 3 x 10(-8), 3 x 10(-6), 3 x 10(-5) mol/ L), and the control confluent cells were cultured in the same medium without steroid. MTT experiment was repeated for 7 days to investigate each groups' cell proliferation. The values of NO were tested as recommended. The tPA and PAI-1 antigen levels were assayed with ELISA Kits. RESULTS: Testosterone at physiologic or lower concentrations (3 x 10(-10) to 3 x 10(-8) mol/L ) had no adverse effect on A490 and NO level, meanwhile, stimulated the secretion of tPA (P < 0.01). However, tPA levels markedly reduced at larger dose (3 x 10(-6) to 3 x 10(-5) mol/L). On the other hand, PAI-1 antigen levels decreased significantly at the testosterone concentrations ranging from 3 x 10(-10) to 3 x 10(-5) mol/L (P < 0.05). CONCLUSION: Testosterone at physiologically relevant concentrations affectively decreased PAI-1, while increased tPA levels, which suggested that testosterone might have beneficial effects on the Human umbilical vein endothelial cells and cardiovascular system to prevent atherosclerosis.