Search

Background: Currently available guidelines contain conflicting recommendations on the management of blood pressure (BP) in patients with diabetes mellitus (DM). Therefore, it is necessary to appraise the guidelines and summarize the agreements and differences among recommendations., Methods: Four databases and the websites of guideline organizations were searched for guidelines regarding BP targets and thresholds for pharmacologic therapy in DM patients, and the included guidelines were appraised with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument., Results: In 6,498 records identified, 20 guidelines met our inclusion criteria with 64.0% AGREE II scores (interquartile range, 48.5% to 72.0%). The scores of the European and American guidelines were superior to those of the Asian guidelines (both adjusted P<0.001). Most of the guidelines advocated systolic BP targets <130 mm Hg (12 guidelines, 60%) and diastolic BP targets <80 mm Hg (14 guidelines, 70%) in DM patients. Approximately half of the guidelines supported systolic BP thresholds >140 mm Hg (10 guidelines, 50%) and diastolic BP thresholds >90 mm Hg (nine guidelines, 45%). The tiny minority of the guidelines provided the relevant recommendations regarding the lower limit of official BP targets and the ambulatory BP monitoring (ABPM)/home BP monitoring (HBPM) targets and thresholds in DM patients., Conclusion: The lower official BP targets (<130/80 mm Hg) in patients with DM are advocated by most of the guidelines, but they contain conflicting recommendations on the official BP thresholds. Moreover, the gaps regarding the lower limit of official BP targets and the ABPM/HBPM targets and thresholds need to be considered by future study.

Background: Hyperglycemia can induce the heart to enter an oxygen-restricted environment, which results in diabetic cardiomyopathy (DCM). Microbiota-derived short-chain fatty acids (SCFAs) affect O 2 consumption and play crucial roles in modulating metabolic and cardiovascular health. The epigenetic regulation of the hypoxia-inducible factor 3A (HIF3A) gene is implicated in oxidative metabolism in the pathogenesis of diabetes. Identifying the associations between plasma SCFA levels and intronic DNA methylation of HIF3A may reveal useful predictors or provide insights into the disease processes of DCM., Methods: In this cross-sectional study, we analyzed plasma SCFA levels, HIF3A expression, and CpG methylation of HIF3A intron 1 in peripheral blood from patients with type 2 diabetes presenting with (n = 92) and without (n = 105) cardiomyopathy., Results: Plasma butyric acid levels and HIF3A mRNA expression in peripheral blood were decreased in DCM patients, whereas 3 CpGs in HIF3A intron 1 (CpG 6, CpG 7 and CpG 11) were highly methylated in DCM patients. Interestingly, butyric acid levels positively correlated with HIF3A levels, while a negative association was identified between butyric acid levels and the methylation rates of HIF3A intron 1 at CpG 6. Butyric acid levels also correlated with several clinical/echocardiographic factors in DCM patients. Additionally, the combination of plasma butyric acid levels and HIF3A intron 1 methylation at CpG 6 discriminated DCM patients from type2 diabetes mellitus (T2DM) patients., Conclusions: The novel associations between plasma butyric acid levels and HIF3A intron 1 methylation at CpG 6 may highlight an underlying mechanism by which the "microbial-myocardial" axis and host-microbe interactions may participate in the pathogenesis of DCM., Competing Interests: Conflicts of interest The authors have declared that no conflict of interest exists., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Doxorubicin (Dox)-induced cardiotoxicity could lead to dilated cardiomyopathy and heart failure. Our previous study reported the protective effects of Klotho against hyperglycemia-induced cardiomyopathy. We investigated whether Klotho alleviated Dox-induced cardiotoxicity. Neonatal rat ventricular cardiomyocytes and H9c2 cells were incubated with 5 μM Dox for 24 h with or without Klotho (0.1 μg/mL). Dox-induced cardiotoxicity model was approached in C57BL/6 mice. Cardiac function and serum enzyme activity, apoptosis and mitochondrial dysfunction were measured. We found that pretreatment with Klotho significantly reduced Dox-induced apoptosis in cardiomyocytes. In Dox-treated mice, Klotho also suppressed cardiac cell death and improved cardiac function. Moreover, the expression of Dynamin-related protein 1 (Drp1) was increased after Dox-treatment both in vitro and in vivo, which was related to apoptosis in cardiomyocytes. In vitro experiments, Drp1 ser 616 phosphorylation post-Dox stimulation could be significantly attenuated by Klotho or Drp1 specific inhibitor Mdivi-1. Overexpression of Drp1 in cardiomyocytes increased Dox-induced heart injury which could also be attenuated by Klotho. This study demonstrated that Klotho alleviated Dox-induced cardiotoxicity by reducing apoptosis and mitochondrial fission through down-regulating Drp1 expression. Our findings highlighted new targets for the therapy of Dox-induced cardiomyopathy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Echocardiography (echo) is the primary imaging modality for infective endocarditis (IE). However, the recommendations on timing and mode selection for transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE) vary across guidelines, which can be confusing for clinical decision makers. In this case, we aim to appraise the quality of recommendations by appraising the quality of various guidelines., Methods: A search of guidelines containing recommendations for the appropriate use of echo in adult IE patients published in English between 2007 and 2019 was conducted. The APPRAISAL OF GUIDELINES FOR RESEARCH & EVALUATION II (AGREE II) instrument was applied independently by two reviewers to assess the integrated quality of the identified guidelines. The recommendations of concern are extracted from related chapters., Results: A total of 9 guidelines met the criteria, with AGREE II scores ranging from 36 to 79%, and the domain of "stakeholder involvement" received the lowest score. The most contentious issue is whether a follow-up TEE is mandatory in uncomplicated native valve IE with an initial positive TTE. Conflicting recommendations are presented with a low evidence level based on little evidence., Conclusions: In general, the recommendations proposed in the 9 identified guidelines on the appropriate use of echo are satisfying. The guideline quality score can be taken into account by the clinicians when evaluating the recommendations for clinical decisions. Additional studies with high evidence level should be conducted on the most controversial issues of whether a subsequent TEE is mandatory in uncomplicated native valve IE with an initial positive TTE.

The effect of renin-angiotensin-aldosterone system (RAAS) blockers [angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers] on Contrast-induced nephropathy (CIN) is unclear in patients with renal insufficiency. Thus, we conduct a meta-analysis to evaluate the association between the administration of RAAS blockers and CIN in patients with renal insufficiency. We searched PubMed, EMBASE, and Cochrane Library for relevant studies published before September 2019. The primary outcome was the incidence of CIN, and the secondary outcome was the changes in serum creatinine (SCr) from baseline to postprocedure (ΔSCr). Pooled odds ratio (OR) or weighted mean difference (WMD) with their 95% confidence interval (CIs) for the CIN incidence, ΔSCr were used to calculate original data. A total of 8 studies were included in the meta-analysis. Compared with controls, ACEI/angiotensin receptor blocker increased the risk of CIN (OR = 1.61, 95% CI 1.14-2.28, I = 30%; P = 0.007), whereas this association was not significant in Chinese patients (OR = 1.07, 95% CI 0.65-1.77, I = 19%, P = 0.79). The total weighted mean differences of the ΔSCr were 0.06 mg/dL (95% CI: 0.01-0.11, I = 82%; P = 0.03). Administration of RAAS blockers in patients with renal insufficiency was associated with a significantly higher incidence of CIN, whereas it did not show a significant effect on Chinese patients.

Background: The pathogenesis of peripheral artery disease (PAD) is associated with impaired calf muscle. We sought to investigate the association between gender-specific calf girth and the prevalence of PAD among participants from a community-based cohort study., Methods: A total 13,808 participants in the Atherosclerosis Risk in Communities (ARIC) study without prior PAD were included in the final analysis. Calf girth was measured at baseline (1985-1987). A hospital diagnosis with an ICD-9 code defined incident PAD during follow up. Cox regression analysis adjusted for demographic variables and other covariates was used to estimate hazard ratios (HR) and 95% confidence interval (CI) for the association between calf girth and PAD., Results: After a medium follow-up of 25.2 years, the overall prevalence of PAD in our study was 5.2% (721/13,808), 335 patients were women and 386 were men. The adjusted HR for PAD with calf girth as continuous variables was 0.99 (95% CI 0.95-1.04) in females and 0.93 (95% CI 0.88-0.99) in males, respectively. Moreover, interaction for gender was statistically significant between calf girth and PAD in overall population (p=0.001)., Conclusions: Our findings revealed a linear association of calf girth with the prevalence of PAD among male participants in ARIC., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine whether the effects of intensive (< 120 mmHg) compared with standard (< 140 mmHg) systolic blood pressure (SBP) treatments are different among those with different baseline SBP., Methods: De-identified SPRINT database was used for this post hoc analysis. SPRINT participants were categorized by baseline SBP status, defined as high-SBP (≥ 140 mmHg) group versus the low-SBP (< 140 mmHg) group. The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Treatment-related adverse events including hypotension, syncope, and bradycardia were also evaluated. Cox regression was used to calculate hazard ratios for study outcomes with intensive compared with standard SBP treatment between these two groups., Results: Among 9361 participants randomized (age 67.9 ± 9.4 years; 35.5% female), 4964 and 4397 had baseline low SBP (< 140 mmHg) and high SBP (≥ 140 mmHg), respectively. After a median follow-up of 3.26 years, the hazard ratio for the primary outcome was 0.65 (95% CI 0.50, 0.83) and 0.84 (95% CI 0.66, 1.06) among those in the low-SBP group and high-SBP group, respectively (P value for interaction 0.15). For treatment-related adverse events, the hazard ratio with intensive SBP treatment was 2.03 (95% CI 1.44, 2.85) for the low-SBP group and 1.80 (95% CI 1.32, 2.47) for the high-SBP group (P value for interaction 0.28)., Conclusions: Hypertensive patients with low baseline SBP may benefit from intensive SBP lowering, whereas benefits were inconclusive among those with high baseline SBP.

Background and Aims: Peripheral arterial disease (PAD) is a clinical manifestation of extracoronary atherosclerosis. Many risk factors are involved in the process of PAD, but the association between serum magnesium (Mg) and PAD is not clear. Our study aimed to investigate whether serum Mg is associated with PAD incidence., Methods: A total of 13,826 participants (aged 40-64 years) in the Atherosclerosis Risk in Communities (ARIC) study (1987-1989) without prior PAD were included in the final analysis. Serum Mg levels were measured at visits 1 and 2. PAD was defined as an ankle brachial index less than 0.9, or hospitalization with a PAD diagnosis. Cox regression was used to calculate hazard ratios (HRs) for incidence of PAD and serum Mg., Results: During a median follow-up of 24.4 years, 1364 (48.4% female) PAD events were observed. After multiple adjustment, participants in the lowest (≤1.4 mEq/L) category of serum Mg compared with the highest (≥1.8 mEq/L) ones were at higher PAD risk (HR: 1.3; 95% confidence interval (CI): 1.06-1.58) (p value = 0.004). The HRs for PAD in 1.5, 1.6 and 1.7 mEq/L of serum Mg were 1.29 (95% CI: 1.08-1.54), 1.05 (95% CI: 0.89-1.24), and 1.0 (95% CI: 0.85-1.18), respectively., Conclusions: Low serum Mg was independently associated with an increased prevalence of PAD in the large population-based study; further studies are needed to confirm our findings., (Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: An environment-wide association study (EWAS) may be useful to comprehensively test and validate associations between environmental factors and cardiovascular disease (CVD) in an unbiased manner., Approach and Results: Data from National Health and Nutrition Examination Survey (1999-2014) were randomly 50:50 spilt into training set and testing set. CVD was ascertained by a self-reported diagnosis of myocardial infarction, coronary heart disease or stroke. We performed multiple linear regression analyses associating 203 environmental factors and 132 clinical phenotypes with CVD in training set (false discovery rate < 5%) and significant factors were validated in the testing set (P < 0.05). Random forest (RF) model was used for multicollinearity elimination and variable importance ranking. Discriminative power of factors for CVD was calculated by area under the receiver operating characteristic (AUROC). Overall, 43,568 participants with 4084 (9.4%) CVD were included. After adjusting for age, sex, race, body mass index, blood pressure and socio-economic level, we identified 5 environmental variables and 19 clinical phenotypes associated with CVD in training and testing dataset. Top five factors in RF importance ranking were: waist, glucose, uric acid, and red cell distribution width and glycated hemoglobin. AUROC of the RF model was 0.816 (top 5 factors) and 0.819 (full model). Sensitivity analyses reveal no specific moderators of the associations., Conclusion: Our systematic evaluation provides new knowledge on the complex array of environmental correlates of CVD. These identified correlates may serve as a complementary approach to CVD risk assessment. Our findings need to be probed in further observational and interventional studies., (Copyright © 2018. Published by Elsevier Ltd.)

Background: This study aimed to investigate the effect of acute kidney injury (AKI) on the progression of renal disease and to develop a clinico-pathological nomogram to predict the renal outcome of IgA nephropathy (IgAN) patients, based on Oxford classification score., Methods: This is a retrospective observational study. A total of 988 IgAN patients treated at our hospital between 2006 and 2011 were included and divided into AKI (n = 82) and non-AKI group (n = 906). The primary outcome measure was the composite renal endpoint. The secondary outcome measure was all-cause mortality. Clinical and pathologic features were assessed with multivariable Cox regression to predict the outcome in IgAN patients. A nomogram was developed to predict the renal outcome., Results: The median follow-up time was 48.6 months (range: 34.4 to 62.7). The incidence of AKI was 8.30%. The AKI group had more severe pathological characteristics and a significantly poor survival outcome than the non-AKI group. The multivariate Cox regression analysis showed that the AKI group had a 2.84 times higher risk of the composite renal endpoint as compared with the non-AKI group (P < 0.001). A clinico-pathological nomogram was developed using the seven predictors for the primary renal composite endpoint. The AUC for the nomogram model was 0.81 (sensitivity = 0.78, specificity = 0.85), and the C-index was 0.91 (95% CI = 0.85-0.97)., Conclusions: For IgAN patients, AKI is an independent risk factor for the progression of renal disease. Our nomogram model has good prediction power for the renal outcome of IgAN patients., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background and Aims: An environment-wide association study (EWAS) may be useful to comprehensively test and validate associations between environmental factors and peripheral arterial disease (PAD) in an unbiased manner., Methods: Data from cross-sectional cohorts from the US National Health and Nutrition Examination Survey (1999-2004) were randomly 50:50 split into training set and testing set. A value of ankle-brachial index (ABI) <1.0 or >1.4 defined PAD. We performed multiple linear regression analyses associating each of the 417 environmental and self-reported factors with PAD in the training set (false discovery rate <5%). Significant findings were validated in the testing set (p < 0.05) and entered into a logistic regression model with penalized likelihood based on the Akaike Information Criterion (AIC)., Results: Overall, 6819 participants >40 years old were included. The validated factors comprised positive associations with smoking-associated factors (cigarette smoker, family smoker and smoked >100 cigarettes, urinary cotinine), cadmium, urinary albumin, C-reactive protein, blood o-xylene and thyroxine 4, and inverse associations with α-carotene and trans-/cis-β-carotene for PAD. Finally, only 4 of these factors were nominally significant in the AIC-selected model: cadmium (OR 1.27, 95% CI 1.12-1.45), cis-β-carotene (OR 0.81, 95% CI 0.72-0.91), CRP (OR 1.19, 95% CI 1.03-1.38) and urinary albumin (OR 1.20, 95% CI 1.04-1.38)., Conclusions: Our systematic evaluation provides new knowledge on the complex array of environmental correlates of PAD. These identified correlates need to be probed in further observational and interventional studies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Atherosclerosis (AS) induced by endothelial cell (EC) dysfunction significantly contributes to the onset and development of cardiovascular disease. Pitavastatin is a member of the lipid-lowering drugs, statins that are widely used in clinics. In the current study, we evaluated the effect of pitavastatin on AS and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in abdominal aortic ECs. We induced AS in rabbits by high-cholesterol diet plus balloon catheter injury. The anti-AS effect of pitavastatin was assessed by measuring the intima-media thickness of the abdominal aorta, minimal lumen area (MLA), minimal lumen diameter (MLD), and other hemodynamic parameters. In addition, we measured the production of total cholesterol (CHOL, high density lipoproteins (HDL), low-density lipoprotein cholesterol (LDL-c), and triglycerides (TG) in the rabbits. To explore the underlying mechanism of pitavastatin on atherosclerosis, we isolated abdominal aortic ECs and determined the activity of NF-κB signaling. In our model, we found that the affected animals had structural impairments of the heart and arteries: reduced left atrium diameter, right ventricular internal diameter, MLA, and MLD and increased interventricular septal thickness, left ventricular internal diameter, left ventricular posterior wall thickness, right atrium diameter, and intima-media thickness of abdominal aorta. Most of these changes were restored by administration of pitavastatin. Moreover, concentrations of plasma lipids were also attenuated by pitavastatin. At the molecular level, pitavastatin inhibited the expression of NF-κB and Bax and induced the production of IL-1β and Bcl-2. In addition, we demonstrated that the anti-AS effect of pitavastatin depends on restoring normal function of ECs and eliminating dysfunctional ECs by inducing apoptosis., Competing Interests: None., (IJCEP Copyright © 2018.)

Cardiac inflammation and oxidative stress play a key role in the pathogenesis of diabetic cardiomyopathy (DCM). The anti-aging protein Klotho has been found to protect cells from inflammation and oxidative stress. The current study aimed to explore the cardioprotective effects of Klotho on DCM and the underlying mechanisms. H9c2 cells and neonatal cardiomyocytes were incubated with 33mM glucose in the presence or absence of Klotho. Klotho pretreatment effectively inhibited high glucose-induced inflammation, ROS generation, apoptosis, mitochondrial dysfunction, fibrosis and hypertrophy in both H9c2 cells and neonatal cardiomyocytes. In STZ-induced type 1 diabetic mice, intraperitoneal injection of Klotho at 0.01mg/kg per 48h for 3months completely suppressed cardiac inflammatory cytokines and oxidative stress and prevented cardiac cell death and remodeling, which subsequently improved cardiac dysfunction without affecting hyperglycemia. This study revealed that Klotho may exert its protective effects by augmenting nuclear factor erythroid 2-related factor 2 (Nrf2) expression and inactivating nuclear factor κB (NF-κB) activation both in vitro and in vivo. Thus, this work demonstrated for the first time that the anti-aging protein Klotho may be a potential therapeutic agent to treat DCM by inhibiting oxidative stress and inflammation. We also demonstrated the critical roles of the Nrf2 and NF-κB pathways in diabetes-stimulated cardiac injuries and indicated that they may be key therapeutic targets for diabetic complications., (Copyright © 2017. Published by Elsevier B.V.)

Cardiac resynchronization therapy can treat chronic heart failure through either biventricular pacing (BVP) or isolated left ventricular pacing (LVP), and the efficacy is depended on QRS duration. However, the optimal therapeutic choice of pacing or how the QRS influences the efficacy remains uncertain. To investigate this uncertainty, we searched available publications in PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials databases regarding differentials in efficacy parameters between BVP and LVP. A meta-analysis of eight randomized controlled trials found that BVP and LVP were comparable with regard to quality-of-life scores, left ventricular ejection fraction, left ventricular end-systolic volume, and mortality or heart transplant rates. However, there was a significant heterogeneity among the trials in 6-min walking distances. Subsequent meta-regression indicated that the baseline QRS duration significantly correlated with the standard mean difference between BVP and LVP. As QRS duration increased, the gain in 6-min walking distance with BVP became significantly greater than that of LVP. This suggests that it is necessary to consider the QRS duration when comparing the clinical effects of BVP and LVP.

The hypoxia-induced proliferation of pulmonary artery smooth muscle cells (PASMCs) is the main cause of pulmonary arterial hypertension (PAH), in which oxidative stress, cyclooxygenase (COX)-2 and hydrogen sulfide (H(2)S) all play an important role. In the present study, we aimed to examine the effects of H(2)S on the hypoxia-induced proliferation of human PASMCs (HPASMCs) and to elucidate the underlying mechanisms. The HPASMCs were treated with cobalt chloride (CoCl(2)), a hypoxia-mimicking agent, to establish a cellular model of hypoxic PAH. Prior to treatment with CoCl(2), the cells were pre-conditioned with sodium hydrosulfide (NaHS), a donor of H(2)S. Cell proliferation, reactive oxygen species (ROS) production, COX-2 expression, prostacyclin (also known as prostaglandin I2 or PGI(2)) secretion and H(2)S levels were detected in the cells. The exposure of the HPASMCs to CoCl(2) markedly increased cell proliferation, accompanied by a decrease in COX-2 expression, PGI(2) secretion and H(2)S levels; however, the levels of ROS were not altered. Although the exogenous ROS donor, H(2)O(2), triggered similar degrees of proliferation to CoCl(2), the ROS scavenger, N-acetyl-L-cysteine (NAC), markedly abolished the H(2)O(2)‑induced cell proliferation, as opposed to the CoCl(2)-induced proliferation. The CoCl(2)-induced proliferation of HPASMCs was suppressed by exogenously applied PGI(2). The addition of H(2)S (NaHS) attenuated the CoCl(2)-induced cell proliferation through the increase in the intercellular content of H(2)S. Importantly, the exposure of the cells to H(2)S suppressed the CoCl(2)-induced downregulation in COX-2 expression and PGI(2) secretion from the HPASMCs. In conclusion, the results from the current study suggest that H(2)S enhances hypoxia-induced cell proliferation through the upregulation of COX-2/PGI(2), as opposed to ROS.

Angiotensin (Ang)-(1-7) exhibits cardioprotective effects in myocardial ischemia reperfusion (I/‌R)-induced injury. However, the roles of oxidation and cyclooxygenase (COX) in the cardioprotection of Ang-(1-7) remain unclear. This study was conducted to investigate whether oxidation and COX were involved in the cardioprotection of Ang-(1-7) against I/‌R-induced injury in isolated rat hearts. The hearts were subjected to 15 min regional ischemia followed by 30 min reperfusion. Myocardial I/‌R treatment induced significant cardiac dysfunction, including ventricular arrhythmia (VA) and a reduction of left ventricular systolic pressure (LVSP), cardiomyocyte apoptosis and oxidative stress, manifesting as an increase in malondialdehyde (MDA) production and a decrease in superoxide dismutase (SOD) activity. Pretreatment of the hearts with 1.0 nmol/‌l Ang-(1-7) for 30 min prior to ischemia considerably attenuated I/‌R-induced VA, apoptosis and MDA production, and enhanced LVSP and SOD activity. These cardioprotective effects of Ang-(1-7) were antagonized by the intraperitoneal injection of 5 mg/‌kg body weight indomethacin (IDM, a COX inhibitor), presenting as an enhancement of VA, apoptosis and MDA production as well as a reduction of LVSP and SOD activity. In conclusion, COX mediated Ang-(1-7)-induced cardioprotection via its antioxidative mechanism.

The present study evaluated potential mechanisms of hydrogen sulfide (H2S)-mediated cardioprotection using an in vitro chemical hypoxia-induced injury model. We have demonstrated that H2S protects H9c2 cardiomyoblasts (H9c2) against chemical hypoxia-induced injuries by suppressing oxidative stress and preserving mitochondrial function. The aim of this study was to investigate the role of heat shock protein 90 (HSP90) in cardioprotection of H2S in H9c2 cells. The findings of the present study showed that cobalt chloride (CoCl2), a chemical hypoxia agent, significantly enhanced the expression of HSP90 and that 17-allylamino-17-demethoxy geldanamycin (17-AAG), a selective inhibitor of HSP90, aggravated concentration-dependent cytotoxicity induced by CoCl2. Exogenous administration of NaHS (a donor of H2S) augmented not only HSP90 expression under normal conditions, but also CoCl2-induced overexpression of HSP90. Pre-treatment with 17-AAG significantly blocked the cardioprotection of H2S against CoCl2-induced injuries, leading to increases in cytotoxicity and apoptotic cells. Furthermore, pre-treatment with 17-AAG also antagonized the inhibitory effects of NaHS on overproduction of reactive oxygen species (ROS), a loss of mitochondrial membrane potential (MMP) and ATP depletion induced by CoCl2. In conclusion, these results demonstrate that the increased expression of HSP90 may be one of the endogenous defensive mechanisms for resisting chemical hypoxia-induced injury in H9c2 cells. We also provide novel evidence that HSP90 mediates the cardioprotection of H2S against CoCl2-induced injuries by its antioxidant effect and preservation of mitochondrial function in H9c2 cells.

Objectives: The objectives were to study the effects of an ACE inhibitor on the force-frequency relationship (FFR) and its possible mechanism in isolated failing myocytes., Methods and Results: Male Wistar rats were randomized into a heart failure group treated with perindopril (CHF-T, 3 mg.kg(-1)d-1), a heart failure group without treatment (CHF-C) and a sham-operated group (PS). Heart failure was induced by constriction of the abdominal aorta. All groups were further followed up for 12 weeks. Left ventricular myocytes were isolated. Cell-shortening fraction (FS) and intracellular calcium transients were measured at different frequency field stimulations. A negative force-frequency relationship (FFR) was found in the CHF-C group compared with the positive-negative biphasic FFR in the PS group, and a flat FFR in the CHF-T group. Intracellular Ca2+ frequency relationships (CaFRs) were positive-negative biphasic in both the PS and CHF-T groups, whereas a negative CaFR was found in the CHF-C group. Regardless of the stimulation frequency, FS significantly correlated with [Ca2+]imax in the PS or CHF-C groups. Compared to the PS group, protein levels of SERCA2 significantly decreased and NCX1 increased in the CHF-C group. In the CHF-T group, these changes were reduced., Conclusion: The ACE inhibitor could improve the impaired FFR of isolated failing myocytes. This effect was possibly mediated via ameliorating the disturbance of CaFR.

Objective: To investigate elastic changes of the radial artery, a medium-sized muscular peripheral conduit artery, in patients with borderline systolic hypertension., Methods: Using a non-invasive high-resolution echo-tracking device coupled to a photoplethysmography (Finapres system) allowing simultaneous arterial diameter and finger blood pressure monitoring, we measured radial artery elastic parameters of 20 patients with borderline systolic hypertension and 20 normal subjects according to Langewouters model., Results: The diameter of the radial artery of control subjects and those with borderline systolic hypertension at the isobaric level of 100 mmHg and mean arterial pressure was similar, but the compliance and distensibility at similar conditions in patients with borderline systolic hypertension did not further reduced and even increased., Conclusion: In patients with borderline systolic hypertension, the adaptive responses of the radial artery compliance and distensibility to increased pressure were directed to maintain its elasticity, contributing to the homeostasis of the cardiovascular system.