Correlation between left atrial strain and left ventricular diastolic function in hypertensive patients. / å·¦æˆ¿åº”å˜ä¸Žé«˜è¡€åŽ‹æ‚£è€ å·¦å®¤èˆ’å¼ åŠŸèƒ½çš„ç›¸å ³æ€§.

OBJECTIVES: Early detection of asymptomatic diastolic dysfunction is essential to prevent the development of heart failure in hypertensive patients. Current studies suggest that left atrial strain contributes to the evaluation of left ventricular diastolic function, but there are fewer studies on the correlation between left atrial strain and diastolic function in hypertensive patients. In this study, we applied a two-dimensional speckle tracking technique to evaluate the changes in left atrial strain in hypertensive patients, and to investigate the relationship between left atrial strain and left ventricular diastolic function. METHODS: A total of 82 hypertensive patients who were visited the Department of Cardiology at the Third Xiangya Hospital of Central South University from July 2021 to January 2022, were enrolled for this study, and 59 healthy subjects served as a control group. According to the number of left ventricular diastolic function indexes recommended by the 2016 American Society of Echocardiography Diastolic Function Guidelines (mitral annular e´ velocity: Septal e´<7 cm/s, lateral e´<10 cm/s, E/e´ ratio>14, left atrial volume index>34 mL/m2, peak tricuspid regurgitation velocity>2.8 m/s), the hypertensive patients were divided into 3 groups: Group Ⅰ (0 index, n=36 ), Group Ⅱ (1 index, n=39), and Group Ⅲ (2 indexes, n=7). Two-dimensional speckle tracking technique was used to measure left atrial reservoir strain (LASr), conduit strain, and contraction strain, and to analyze the correlation between left atrial strain and left ventricular diastolic function in hypertensive patients. RESULTS: The LASr, left atrial conduit strain (LAScd), and LASr/(E/septal e´) of the hypertension group were lower than those of the control group, and E/LASr was higher than that of the control group. There was no significant difference in left atrium volume index between the 2 groups (P>0.05). Compared with Group Ⅰ, LASr, LAScd, and LASr/(E/septal e´) were decreased in Group Ⅱ and Group Ⅲ, LASr/(E/septal e´) was also decreased in Group Ⅲ compared with Group Ⅱ (all P<0.05). Compared with Group Ⅰ, E/LASr was increased in Group Ⅲ. LASr was positively correlated with septal e´, lateral e´, E, and E/A, and negatively correlated with E/septal e´. CONCLUSIONS: The changes of left atrial function in patients with early hypertension are earlier than those of left atrial structure. Left atrial strain and its combination with conventional ultrasonographic indices [LASr/(E/septal e´)] of diastolic function are potentially useful in assessing left ventricular diastolic function in hypertensive patients.

Initial treatment with a single capsule containing half-dose quadruple therapy vs standard-dose dual therapy in hypertensive patients (QUADUAL): Study protocol for a randomized, blinded, crossover trial.

BACKGROUND: Combined antihypertensive therapy has obvious advantages over single drug therapy. Hypertension guidelines fully affirm the efficacy of dual combination in initial antihypertensive therapy. Recent studies have also pointed out that the quadruple combination of very low-dose antihypertensive drugs is superior to single drugs. However, whether low-dose quadruple therapy is better than dual combination is unknown. OBJECTIVE: To evaluate and compare the efficacy and safety of half-dose quadruple therapy vs standard-dose dual therapy in the initial treatment of hypertensive patients with systolic/diastolic blood pressure 140-179/90-109 mm Hg. METHODS: A randomized double-blind crossover clinical trial will be conducted to compare the efficacy and safety of low-dose quadruple antihypertensives (irbesartan 75 mg + metoprolol 23.75 mg + amlodipine 2.5 mg + indapamide 1.25 mg) with standard-dose dual antihypertensives (irbesartan 150 mg + amlodipine 5 mg) in the initial treatment of patients with mild to moderate hypertension (140-179/90-109 mm Hg). Ninety patients are required and will be recruited and randomly assigned in a 1:1 ratio to 2 crossover groups. Two groups will receive a different combination therapy for 4 weeks, then switch to the other combination therapy for 4 weeks, with a 2-week wash-out. The patients will be followed up for 4 weeks to compare the antihypertensive effects and related adverse effects of the 2 antihypertensive combination treatments. CONCLUSIONS: We present the rationale for the design of the QUADUAL trial. The trial started in July 2022 and is expected to be completed by August 2023. The study aims to evaluate if an initial treatment regimen of quadruple combination of half-dose blood pressure medications will result in greater reduction in blood pressure and fewer side effects compared to standard dose dual therapy. REGISTRATION: www. CLINICALTRIALS: gov (NCT05377203).

Left ventricular systolic function between left bundle branch pacing and right ventricular septum pacing in patients with pacemaker dependence by three-dimensional speckle tracking imaging. / ä¸‰ç»´æ–‘ç‚¹è¿½è¸ªæŠ€æœ¯è¯„ä»·å·¦æŸæ”¯èµ·æã€å³å®¤é—´éš”éƒ¨èµ·æçš„å¿ƒå®¤èµ·æä¾èµ–æ‚£è€ å·¦å¿ƒå®¤æ”¶ç¼©åŠŸèƒ½.

OBJECTIVES: To compare the left ventricular systolic function between the 1eft bundle branch pacing (LBBP) and right ventricular septum pacing (RVSP) in patients with pacemaker dependence by three-dimensional speckle tracking imaging (3D-STI). METHODS: A total of 65 patients with atrioventricular block (AVB) (Mobitz type II second-degree AVB, high-degree AVB, or third-degree AVB), who underwent permanent cardiac pacing implantation including 32 patients receiving LBBP (LBBP group) and 33 patients receiving RVSP (RVSP group) from June 2018 to June 2019,were enrolled in this study. These patients met the following inclusion criterion: pre-operative left ventricular ejection fraction (LVEF)>50% and ventricular pacing rate>40% at 6-month programming follow-up; and the patients underwent echocardiography at pre-operation and 6 months after operation. The 3D-STI was used to obtain global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), and global area strain (GAS). RESULTS: All the patients in the LBBP group and the RVSP group had normal LVEF, there was no significant difference between the 2 group (P>0.05). The LVEF was slightly decreased at 6-month follow-up in the RVSP group, but there was no significant change compared with pre-operation (P>0.05). There were no significant difference in LVEF, GLS, GCS, GRS and GAS at pre-operation and 6-month after operation between the LBBP group and the RVSP group (all P>0.05). Compared with pre-operation, the GLS and GCS were significantly decreased in the LBBP group; while the GLS, GCS, GRS and GAS in the RVSP group were also significantly decreased at 6-month follow-up (all P<0.05). CONCLUSIONS: For patients with pacemaker dependence and normal LVEF at pre-operation, the cardiac function in the LBBP group is not significantly better than that in the RVSP group in short term follow-up. But in terms of physiologic pacing and long-term cardiac function protection, the 1eft bundle branch pacing is an optimal pacing mode.

Renalase improves pressure overload-induced heart failure in rats by regulating extracellular signal-regulated protein kinase 1/2 signaling.

Renalase, a novel flavoprotein that is mainly expressed in the kidney and heart, plays a crucial role in hypertension. Recent studies have shown that renalase is expressed at low levels in the serum of patients with heart failure, while the role of renalase and its mechanism in cardiac failure is unclear. Adult Sprague-Dawley (SD) rats were used to investigate the role and function of renalase in the pathological process of transverse aortic constriction (TAC)-induced heart failure. Renalase-human protein chip analysis showed that renalase was directly associated with P38 and extracellular signal-regulated protein kinase 1/2 (ERK1/2) signaling. We further used lentivirus-mediated RNA interference to study the role of renalase in the progression of pathological ventricular hypertrophy and found that renalase inhibition attenuated the noradrenaline-induced hypertrophic response in vitro or the pressure overload-induced hypertrophic response in vivo. Recombinant renalase protein significantly alleviated pressure overload-induced cardiac failure and was associated with P38 and ERK1/2 signaling. These findings demonstrate that renalase is a potential biomarker of hypertrophy and that exogenous recombinant renalase is a potential and novel drug for heart failure.

Atorvastatin alleviates left ventricular remodeling in isoproterenol-induced chronic heart failure in rats by regulating the RhoA/Rho kinase signaling pathway.

BACKGROUND: Chronic heart failure (CHF) is characterized by left ventricular dysfunction and altered autonomic control of cardiac function. This study aimed to investigate the effects of atorvastatin on left ventricular remodeling (LVR) and cardiac function in rats with isoproterenol-induced CHF and the possible mechanism. METHODS: An isoproterenol-induced CHF model was established in rata, which were subsequently treated with atorvastatin. Echocardiography, hemodynamic, and left ventricular mass indexes were assessed. The mRNA expression of RhoA, Rho kinase, and endothelial nitric oxide synthase (eNOS) was determined by RT-qPCR. The protein expression of myosin-binding subunit (MBS), MBS-P, eNOS, phosphorylated-eNOS, RhoA, and Rho kinase was measured by Western blot analysis. The relative activity of NADPH oxidase, ROS, and NO was assessed by ELISA. RESULTS: Isoproterenol-induced CHF rats treated with atorvastatin exhibited decreased left ventricular end-systolic dimension, left ventricular end-diastolic dimension, left ventricular end-diastolic pressure, left ventricular mass index, maximum fall rate of change in left ventricular pressure, heart rate (p < 0.001), expression of RhoA, Rho kinase, MBS and MBS-P (p < 0.01), and relative activity of NADPH oxidase, ROS and NO (p < 0.05) and increased left ventricular short axis fractional shortening, left ventricular end-systolic pressure, maximum rise rate of change in left ventricular pressure (p < 0.001) and expression of eNOS, and phosphorylated-eNOS ser1177 (all p < 0.05) compared with those of rats with isoproterenol-induced CHF. CONCLUSION: We demonstrated that atorvastatin inhibits LVR and improves cardiac function in rats with isoproterenol-induced CHF through inhibition of the RhoA/Rho kinase signaling pathway.

Effects of arterial blood on the venous blood vessel wall and differences in percentages of lymphocytes and neutrophils between arterial and venous blood.

Vascular sclerosis mostly occurs in arteries and is mainly related to anatomic structure and hemodynamics of artery. This study aimed to investigate effects of arterial blood on vein wall and explore differences of composition between arterial and venous blood.Ultrasound was used to examine the distal venous structure of arteriovenous fistula in uremia patients. Immunohistochemistry was used to study the pathology of the distal vein. Twelve patients were divided into control group and trial group. Patients received an arteriovenous fistula within 1 month in control group. Patients had undergone this surgery ≥2 years before in the trial group. Blood samples were collected from the aortic, arterial, and venous vessels of 51 patients who had taken coronary angiography and analyzed with blood routine rest, biochemical, and immunological measures to compare the differences of blood composition between artery and vein. This study was registered with the China Clinical Trial Center website under registration number ChiCTR-OOC-16008085.In the trial group, the vascular wall of distal veins of fistula were thickened and hardened. No significant differences of blood composition were found between the aortic and radial arterial blood. However, the differences in the percentages of lymphocytes and neutrophils between arterial and venous blood were significant (Pa = .0095, Pb = .01).Under smooth hemodynamic conditions, arterial blood caused hardening of the venous wall. Arterial and venous blood differed in the percentage of lymphocyte and neutrophils. This may contribute to the vascular sclerosis that is observed in arteries more often than veins.

PAI-1 4G/5G polymorphism and coronary artery disease risk: a meta-analysis.

Many epidemiologic studies have investigated the plasminogen activator inhibitor-1 (PAI-1) gene 4G/5G polymorphism and this association with coronary artery disease (CAD). But definite conclusions can not be drawn. Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) till 10 August 2014. Pooled ORs and 95% CIs were used to assess the strength of the associations. A total of 53 studies including 20921 CAD cases and 18434 controls were included. Significantly elevated CAD risk was found in overall analysis (OR = 1.13, 95% CI: 1.05-1.21, P = 0.0009). In the subgroup analysis by races, significantly increased risk was found in Caucasians (OR = 1.11, 95% CI: 1.03-1.20, P = 0.005) and Asians (OR = 1.20, 95% CI: 1.01-1.42, P = 0.04). In the subgroup analysis by gender, significant association was found in males (OR = 1.15, 95% CI: 1.06-1.25, P = 0.0008), but was not found in females (OR = 1.05, 95% CI: 0.92-1.20, P = 0.47). In the subgroup analysis by age, young populations showed increased CAD risk (OR = 1.19, 95% CI: 1.02-1.37, P = 0.02), but old populations did not show this association (OR = 1.01, 95% CI: 0.82-1.24, P = 0.93). This meta-analysis provides the evidence that PAI-1 4G/5G polymorphism may contribute to the CAD development.

Triptolide improves systolic function and myocardial energy metabolism of diabetic cardiomyopathy in streptozotocin-induced diabetic rats.

BACKGROUND: Triptolide treatment leads to an improvement in Diabetic Cardiomyopathy (DCM) in streptozotocin-induced diabetic rat model. DCM is characterized by abnormal cardiac energy metabolism. We hypothesized that triptolide ameliorated cardiac metabolic abnormalities in DCM. We proposed (31)P nuclear magnetic resonance ((31)P NMR) spectrometry method for assessing cardiac energy metabolism in vivo and evaluating the effect of triptolide treatment in DCM rats. METHODS: Six weeks triptolide treatment was conducted on streptozotocin-induced diabetic rats with dose of 100, 200 or 400 µg/kg/day respectively. Sex- and age-matched non-diabetic rats were used as control group. Cardiac chamber dimension and function were determined with echocardiography. Whole heart preparations were perfused with Krebs-Henseleit buffer and (31)P NMR spectroscopy was performed. Cardiac p38 Mitogen Activating Protein Kinase (MAPK) was measured using real time PCR and western blot analysis. RESULTS: In diabetic rats, cardiac mass index was significantly higher, where as cardiac EF was lower than control group. (31)P NMR spectroscopy showed that ATP and pCr concentrations in diabetic groups were also remarkably lower than control group. Compared to non-treated diabetic rats, triptolide-treated diabetic groups showed remarkable lower cardiac mass index and higher EF, ATP, pCr concentrations, and P38 MAPK expressions. Best improvement was seen in group treated with Triptolide with dose 200 µg/kg/day. CONCLUSIONS: (31)P NMR spectroscopy enables assessment of cardiac energy metabolism in whole heart preparations. It detects energy metabolic abnormalities in DCM hearts. Triptolide therapy improves cardiac function and increases cardiac energy metabolism at least partly through upregulation of MAPK signaling transduction.

Renalase protects the cardiomyocytes of Sprague-Dawley rats against ischemia and reperfusion injury by reducing myocardial cell necrosis and apoptosis.

BACKGROUND/AIMS: Renalase, a novel flavoprotein expressed in the kidney and heart, reduces renal tubular necrosis and apoptosis, which suggests that it might protect against necrosis and/or apoptosis in myocardial ischemia reperfusion injury (MIRI). The present study thus explored the effects of renalase on Sprague-Dawley (SD) rats subjected to MIRI. METHODS: We used Lentivirus-mediated RNA interference (RNAi) to inhibit the renalase gene expression in the heart tissue via pericardial cavity injection. The MIRI animal modal was established by blocking the left anterior descending artery for 45mins followed by 4h of reperfusion. Real-time PCR and western blotting were used to detect renalase expression in the heart tissue. Double staining and TUNEL were used to detect the necrosis and apoptosis in the myocardial cells, respectively. RESULTS: All rats subjected to MIRI exhibited lower levels of renalase in the heart tissue than did the sham-operated group (P<0.05, n=6). The (RNAi) group rats exhibited lower renalase levels than did the controls and also exhibited more serious necrosis (7.12±0.56% vs. 3.32±0.93%, P<0.05, n=6) and apoptosis (151.8±8.2% vs. 66.8±6.5%, P<0.05, n=6); however, pretreatment with the recombinant renalase significantly reduced myocardial cell necrosis (1.51±0.12% vs. 4.13±0.02%, P<0.05, n=6) and apoptosis (21.3±5.0% vs. 52.6±10.4%, P<0.05, n=6) relative to the control rats. CONCLUSIONS: Exogenous recombinant renalase protein reduced myocardial cell necrosis and apoptosis. Recombinant renalase protein might be a new cardiovascular drug for ischemia/IR injury.

[Effect of Tip30 expression on the invasion and metastasis of hepatoma cells].

OBJECTIVE: To investigate the effect of Tip30 on the invasion and metastasis of hepatoma cells. METHODS: Recombinant plasmid pAAV-Tip30 was transfected to HepG2 cells by polylactic-coglycolic acid (PLGA) nanoparticles. RT-PCR was used to detect the mRNA expression of matrix metalloproteinases (MMP)-2, MMP-9 and epidermal growth factor receptor (EGFR). MMP- 2 and MMP-9 protein level in the tumor tissue was detected by Western blot. The proliferation, of hepatoma cells was evaluated by MTS assay and clone formation method. The adhesion and invasion of hepatoma cells were evaluated by adhesion assay and Transwell migration assay, respectively. RESULTS: With RT-PCR and Western blot, we found Tip30 decreased the expression of MMP-2 and MMP-9. MTS assay and cell clone formation method showed inhibited proliferation of the HepG2 cells. Chemo invasion assays showed that Tip30 decreased the invasiveness of hepatoma cells. Tip30 attenuated the binding of liver cancer cell line to human umbilical vein endothelial cells and fibronectin. CONCLUSION: The invasion and metastasis of hepatoma cells can be inhibited by Tip30 gene in vitro.

Renalase, a new secretory enzyme: Its role in hypertensive-ischemic cardiovascular diseases.

Abstract Renalase, a novel amine oxidase, is mainly expressed in the kidney, heart, and skeletal muscle. It has been known to degrade circulating catecholamines and plays a crucial role in human diseases. Recent studies have demonstrated its structure, unique bioactivities, function, and the gene polymorphisms in human diseases. In this review, we summarize the effects of renalase on hypertension, myocardial ischemia, acute kidney injury (AKI), ischemic stroke, cardiac dysfunction, organ transplantation, and diabetes mellitus reported in numerous studies.

Anti-inflammatory effects of triptolide improve left ventricular function in a rat model of diabetic cardiomyopathy.

AIMS: Given the importance of inflammation in the onset and progression of diabetic cardiomyopathy, we investigated the potential protective effects of triptolide, an anti-inflammatory agent, in streptozotocin-induced diabetic rat model and in H9c2 rat cardiac cells exposed to high glucose. METHODS AND RESULTS: Diabetic rats were treated with triptolide (100, 200, or 400 µg/kg/day respectively) for 6 weeks. At the end of this study, after cardiac function measurements were performed, rats were sacrificed and their hearts were harvested for further histologic and molecular biologic analysis. Enhanced activity and expression of nuclear factor-kappaB (NF-κB) p65 in diabetic hearts were associated with increased inflammatory response, as demonstrated by increased pro-inflammatory cytokines, cell adhesion molecules and invading inflammatory cells, as well as increased fibrosis, in line with impaired left ventricular function. Triptolide attenuated these morpho-functional alterations. Furthermore, triptolide (20 ng/ml) also attenuated high glucose-induced inflammation in H9c2 rat cardiac cells. CONCLUSION: Our data demonstrate that anti-inflammatory effects of triptolide involving the NF-κB signaling pathway can improve left ventricular function under diabetic conditions, suggesting triptolide treatment might be beneficial in diabetic cardiomyopathy.

Feasibility of detecting early left ventricular systolic dysfunction using global area strain: a novel index derived from three-dimensional speckle-tracking echocardiography.

AIMS: Area strain (AS), derived from three-dimensional speckle-tracking echocardiography (3D-STE), is a novel parameter integrating longitudinal and circumferential deformation. We sought to evaluate the ability of global AS to detect early left ventricular (LV) systolic dysfunction in patients with risk factors for heart failure (HF). METHODS AND RESULTS: Standard echocardiography and 3D-STE were performed in 160 subjects with or without HF. Three-dimensional speckle-tracking echocardiography was measured with reliable tracking quality in 137 (86%) of the 160 subjects initially enrolled in this study: 30 healthy volunteers, 29, 37, 26, and 15 patients with Stage A, B, C, and D HF, respectively. Global strain values were automatically calculated by 3D wall motion tracking (3D-WMT) software. Although global longitudinal strain (LS), circumferential strain (CS), radial strain (RS), and LV ejection fraction (LVEF) showed the downward trend from normal controls to patients with Stage D HF, the difference did not reach statistical significance between normal controls and patients with Stage A HF. In contrast, we observed the progressive decrease in global AS from normal to Stage A HF to Stage D HF (P< 0.05). In addition, global AS showed an excellent correlation with LVEF, global LS and CS. The optimal cut-off value for global AS, to detect LV dysfunction (Simpson's rule-based LVEF <50%), was -29.23% at a sensitivity of 86.3% and at a specificity of 88.4%. CONCLUSION: Global AS is a sensitive and reproducible parameter to detect early and subtle LV systolic dysfunction, showing greater feasibility than other conventional strain parameters.

[Effect of IL-10 on LOX-1 expression of peripheral blood monocytes in patients with acute coronary syndrome].

OBJECTIVE: To determine the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) of peripheral blood monocytes in patients with acute coronary syndromes (ACS),and to further explore the effect of anti-inflammatory factor interleukin-10 (IL-10) on the expression of LOX-1. METHODS: Twenty-eight healthy controls and 28 ACS patients were enrolled in the study. The levels of IL-10 and tumor necrosis factor (TNF-alpha) were determined by enzyme-linked immunosorbnent assay(ELISA). The monocytes of peripheral blood in patients and controls were isolated and incubated with exogenous IL-10 (20 microg/L). The expression of LOX-1 protein and mRNA in the monocytes was examined by Western blot and reverse transcriptase PCR (RT-PCR). RESULTS: Compared with the healthy controls, the levels of serum IL-10 and TNF-alpha were significantly elevated in ACS patients (P<0.01). The expression of LOX-1 protein and mRNA was markedly upregulated in the isolated monocytes from ACS patients, which could be downregulated by IL-10 (20 microg/L, 3 h) (P<0.01). CONCLUSION: The effect of anti-inflammatory factor IL-10 on the atherosclerosis may be a new mechanism resulting in plaque stabilization via the decreased LOX-1 expression of peripheral monocytes in ACS patients.

[Proatherogenic effects of immune complexes of human oxLDL in vitro].

OBJECTIVE: To observe the effects of immune complexes (IC) prepared from human oxidized density lipoprotein (oxLDL) antibodies and human oxLDL on the foam cell forming and the macrophage activation, and to further uncover the possible mechanisms of immune complexes contributing to the atherosclerosis occurrence. METHODS: The immune complexes of human oxLDL and purified human oxLDL antibodies were added to culture U937 cells by protocols: polyethylene glycol-precipitated insoluble IC (PEG-IC) and IC immobilized by absorption to red blood cells (RBC-IC). With oxLDL as controls and heat-aggregated gamma globulin as an inhibitor of Fc gamma receptor, we measured the cholesterol ester, total cholesterol of the cellular extracts, and quantified the secreted MMP-1 of supernatants from U937 cells. RESULTS: A significant increase of MMP-1 release [(0.769 +/- 0.030) ng/ml vs (0.513 +/- 0.034) ng/ml, P < 0.01] and a higher level of cholesterol ester accumulation [(20.271 +/- 1.668) microg/mg protein vs (17. 226 +/- 1.298 ) microg/mg protein, P < 0.05] in U937 cells incubated with RBC-IC were observed, compared with those incubated with RBC-oxLDL. However, the above quantative difference between the cholesterol ester accumulation induced by oxLDL and insoluble PEG-IC was even more striking, and cholesterol ester accumulation was dosage-dependent. Heat-aggregated gamma globulin (10 mg/ml) as an inhibitor of Fc gamma receptors competitively inhibited cholesterol ester accumulation and decreased PEG-IC stimulating MMP-1 secretion to 71%. CONCLUSION: Immune complexe of ox-LDL can transform macrophages into foam cells and activted macrophages. The immunological function of oxLDL is involved in the process of atherosclerosis occurrence.