Dexpramipexole attenuates myocardial ischemia/reperfusion injury through upregulation of mitophagy.

Reperfusion causes undesirable damage to the ischemic myocardium while restoring the blood flow. In this study, we evaluated the effects of dexpramipexole (DPX) on myocardial injury induced by ischemia/reperfusion (I/R) in-vivo and the hypoxia/reoxygenation (HR) in-vitro and examined the functional mechanisms of DPX. DPX protected cells against H/R-induced mitochondrial dysfunction and prevented H/R damage. Both myocardial infarct size and tissue damage due to I/R was reduced upon DPX treatment. We discovered that DPX enhanced mitophagy in-vivo and in-vitro, which was accompanied by enhanced expression of PINK1 and Parkin. Knock-down of PINK1 and Parkin by specific siRNAs reversed DPX-induced inhibition of myocardial I/R injury. These findings suggest that DPX might protect against myocardial injury via PINK1 and Parkin.

Ultrasound-Mediated Co-Delivery of miR-34a and sPD-1 Complexed with Microbubbles for Synergistic Cancer Therapy.

BACKGROUND: miR-34a was downregulated and PD-L1 was upregulated in cervical cancer; however, the treatment of cervical cancer lacks precision and targeting. This study explored the ultrasound-mediated co-delivery of miR-34a and sPD-1 complexes with microbubbles for synergistic cancer therapy. METHODS: Cationic lipid microbubbles (CLMBs) were prepared by membrane hydration and mechanical oscillation. U14 subcutaneous xenograft mice were injected with CLMBs-loaded sPD-1 and miR-34a combined with ultrasound targeted destruction, and tumor volume and tumor weight of mice were measured. TUNEL apoptosis test and the mRNA expression of apoptosis-related gene Bcl-2 and Bax were analyzed by qRT-PCR. Antitumor immune-related cytokines IFN-γ were investigated by qRT-PCR, LDH Cytotoxicity Assay Kit were performed to test cytotoxic T lymphocytes (CTL). RESULTS: CLMBs were successfully prepared and the plasmid bound to its surface. The tumor volume and weight were specifically decreased by ultrasound-mediated co-delivery of miR-34a and sPD-1 complexes with microbubbles, apoptosis was induced and the apoptosis suppressor gene Bcl-2 was downregulated and proapoptotic gene Bax were upregulated. qRT-PCR analysis revealed that antitumor immunity-related IFN-γ was strongly upregulated in mice, which were treated with CLMBs-loaded sPD-1 and miR-34a combined with ultrasound targeted destruction, and the percentage of CTL was increased. CONCLUSION: These findings from the study demonstrated that CLMBs could deliver miR-34a and sPD-1, combined with ultrasound targeted destruction, could suppress the tumor tissue growing, induce apoptosis and enhance antitumor immunity in U14 subcutaneous xenograft mice.

Spermidine-enhanced autophagic flux improves cardiac dysfunction following myocardial infarction by targeting the AMPK/mTOR signalling pathway.

BACKGROUND AND PURPOSE: Spermidine, a natural polyamine, is abundant in mammalian cells and is involved in cell growth, proliferation, and regeneration. Recently, oral spermidine supplements were cardioprotective in age-related cardiac dysfunction, through enhancing autophagic flux. However, the effect of spermidine on myocardial injury and cardiac dysfunction following myocardial infarction (MI) remains unknown. EXPERIMENTAL APPROACH: We determined the effects of spermidine in a model of MI, Sprague-Dawley rats with permanent ligation of the left anterior descending artery, and in cultured neonatal rat cardiomyocytes (NRCs) exposed to angiotensin II (Ang II). Cardiac function in vivo was assessed with echocardiography. In vivo and in vitro studies used histological and immunohistochemical techniques, along with western blots. KEY RESULTS: Spermidine improved cardiomyocyte viability and decreased cell necrosis in NRCs treated with angiotensin II. In rats post-MI, spermidine reduced infarct size, improved cardiac function, and attenuated myocardial hypertrophy. Spermidine also suppressed the oxidative damage and inflammatory cytokines induced by MI. Moreover, spermidine enhanced autophagic flux and decreased apoptosis both in vitro and in vivo. The protective effects of spermidine on cardiomyocyte apoptosis and cardiac dysfunction were abolished by the autophagy inhibitor chloroquine, indicating that spermidine exerted cardioprotective effects at least partly through promoting autophagic flux, by activating the AMPK/mTOR signalling pathway. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that spermidine improved MI-induced cardiac dysfunction by promoting AMPK/mTOR-mediated autophagic flux.

Diffusion Tensor Imaging Detects Microstructural Differences of Visual Pathway in Patients With Primary Open-Angle Glaucoma and Ocular Hypertension.

Ocular hypertension (OHT), the common situation in adult patients in the outpatients, occurs ∼5% worldwide. However, there are still some practical problems in differentiation of OHT with early primary open-angle glaucoma (POAG) using current standard methods. Application of high resolution diffusion tensor imaging (DTI) enables us to the differentiate axonal architecture of visual pathway between POAG and OHT subjects. Among 32 POAG patients recruited (15 OHT and 14 control subjects), 62.5% of glaucoma were in early stage for the current study. All subjects underwent ophthalmological assessments with standard automated perimetry and optical coherence tomography (OCT). DTI was applied to measure fraction anisotropy (FA) and mean diffusivity (MD) of optic tract (OT), lateral geniculate body (LGN) and optic radiation (OR) using voxel-based analysis. Our data demonstrated that FA values of bilateral OR in POAG were significantly lower in the right or left than that of OHT patients (left OR: 0.51 ± 0.04 vs. 0.54 ± 0.03, p < 0.05; right OR: 0.51 ± 0.05 vs. 0.54 ± 0.03, p < 0.05). In right LGN, MD values were higher in POAG patients compared with OHT subjects (9.81 ± 1.45 vs. 8.23 ± 0.62, p < 0.05). However, no significant difference of all of the DTI parameters was observed between OHT and control subjects. DTI parameters in POAG patients were positively correlated with morphological and functional measurements (p < 0.05). Vertical cup to disc ratio (VCDR) was correlated with ipsilateral FA of OT (p < 0.05), ipsilateral MD of OT (p < 0.05), ipsilateral MD of LGN (p < 0.05), and contralateral MD of OT (p < 0.05). Mean deviation of visual field (MDVF) was correlated with ipsilateral FA of OT (p < 0.05), ipsilateral MD of OT (p < 0.05), and ipsilateral FA of LGN (p < 0.05). Our study demonstrated that DTI can differentiate POAG from OHT subjects in optic pathway, particularly in early POAG, and DTI parameters can quantify the progression of POAG.

Female Sex as a Risk Factor for Ischemic Stroke and Systemic Embolism in Chinese Patients With Atrial Fibrillation: A Report From the China-AF Study.

Background Previous studies have provided conflicting results as to whether women are at higher risk than men for thromboembolism in the setting of atrial fibrillation ( AF ). We investigated whether women with AF were at higher risk of ischemic stroke in the China-AF (China Atrial Fibrillation Registry) Study. Methods and Results A total of 19 515 patients were prospectively enrolled between August 2011 and December 2016 in the China- AF Study. After exclusion of patients receiving anticoagulation or ablation therapy, 6239 patients (2574 women) with results from at least 6 months of follow-up were used for the analysis. Cox proportional hazards models were performed to evaluate whether female sex was an independent risk factor for thromboembolism after multivariate adjustment. The primary outcome was the time to the first occurrence of ischemic stroke or systemic embolism. After a mean follow-up of 2.81±1.46 years, 152 female patients reached the primary outcome, as compared with 172 male patients. Crude incidence rates of thromboembolism between women and men were of borderline statistical significance (2.08 versus 1.68 per 100 patient-years, P=0.058). After multivariable analysis, female sex was not independently associated with an increased thromboembolism risk (hazard ratio 1.09, 95% confidence interval 0.86-1.39). There was no significant difference in thromboembolism risk by sex stratified by age and presence or absence of risk factors ( P for interaction all >0.1). Conclusions Although crude incidence rates of thromboembolism were higher in Chinese female patients with AF compared with male patients, female sex did not emerge as an independent risk factor for thromboembolism on multivariate analysis. Clinical Trial Registration URL : http://www.chictr.org.cn/ . Unique identifier: Chi CTR - OCH -13003729.

Patient-Reported Treatment Satisfaction with Dabigatran versus Warfarin in Patients with Non-Valvular Atrial Fibrillation in China.

BACKGROUND: Anti-coagulant therapy satisfaction for patients with atrial fibrillation is a critical issue, which impacts on their treatment adherence and clinical outcomes. The disadvantages of long-term warfarin treatment are well-described, and novel oral anti-coagulants have become an alternative option. MATERIALS AND METHODS: We compared patient-reported treatment satisfaction with dabigatran versus warfarin in non-valvular atrial fibrillation (NVAF) patients in China. Treatment satisfaction was assessed using the Anti-Clot Treatment Scale (ACTS) questionnaire, which included a 12-item ACTS Burdens scale and a 3-item ACTS Benefits scale. RESULTS: Among 834 patients, 246 patients (29.5%) were taking dabigatran and the others were on warfarin. Propensity score matching was employed to identify 182 patient pairs with balanced baseline characteristics. The global ACTS Burdens score and the global ACTS Benefits score were comparable between the dabigatran and warfarin groups (44.86 ± 3.95 vs. 44.28 ± 3.51, p = 0.423; 11.49 ± 2.92 vs. 11.42 ± 3.03, p = 0.194, respectively). The monthly cost of dabigatran was significantly higher compared with that of warfarin due to a lack of insurance coverage (USD 176.78 ± 9.15 vs. USD 2.49 ± 0.76, p = 0.000). The discontinuation rate of dabigatran was significantly higher than warfarin at the 6-month follow-up (33.5% vs. 19.2%, p = 0.003). Adjusted logistic regression showed that dabigatran was associated with a significant greater odds of non-persistence (odds ratio: 2.13, 95% confidence interval: 1.27-3.59, p = 0.004). CONCLUSION: Dabigatran therapy in patients with NVAF in China associated with no improvement in satisfaction and a higher discontinuation rate compared with warfarin therapy largely due to increased economic burden.

[Clustering of vestibular direction-selective neurons in macaque parieto-insular vestibular cortex].

Neurons with direction-selectivity for vestibular stimuli are found in a number of cortical areas, and neurons in the ventral intraparietal area (VIP) and the dorsal subdivision of the medial superior temporal area (MSTd) of the macaque brain are clustered according to their direction preferences for vestibular signals. This raises the question where the clustering inherits from? Previous work has shown that VIP and MSTd most probably receive vestibular input from the parieto-insular vestibular cortex (PIVC), which processes vestibular signals at the earlier stage. Thus, PIVC is also supposed to show a clustered organization similar to that seen in VIP and MSTd. The present study was aimed to examine clustering properties of vestibular response in PIVC area. To address this issue, we compared the tuning of isolated single unit (SU) with the undifferentiated multiunit (MU) activity of several neighboring neurons recorded from the same microelectrode. When directional tuning was observed in MU activity, the direction preference generally agreed closely with that of a simultaneously recorded SU. These results suggest that PIVC neurons are indeed clustered according to preferred direction for both translational and rotational vestibular stimuli.

[Progress in multisensory integration during self motion processing].

In the daily life, we perceive the world around us by integrating multiple sensory cues (visual, auditory, olfactory, gustatory, tactile, vestibular and proprioceptive) to create a coherent, reliable representation that allows us to interact meaningfully with the environment. The integration of different sensory information is necessary for our perception, motor transformation, decision making, learning and memory. In the past decades, many interdisciplinary researchers have been attracted to the field of multisensory research, and tremendous advances have been made in this field. We review the researches on multisensory integration during self-motion perception in the past decades from the candidate areas, the integration principles and the neural correlation of the behaviors, with the intention to provide a comprehensive source for those interested in understanding the neural substrates for multisensory integration. Meanwhile, we also provide a prospect for the future research in this field.

MiR-34a and miR-206 act as novel prognostic and therapy biomarkers in cervical cancer.

BACKGROUND: Recent evidence indicated that the aberrant expression of microRNA plays a crucial role in the development of cervical cancer. The overall shorter survival was strongly related to the abnormal expression of microRNA-34a (miR-34a) and microRNA-206 (miR-206), which target B cell lymphoma-2(Bcl2) and c-Met. Hepatocyte growth factor (HGF)/c-Met pathway is related to the occurrence, development and prognosis of cervical cancer, and c-Met is significantly overexpressed in cervical squamous cell carcinoma. Bcl2 is also considered to be a promising target for developing novel anticancer treatments. METHODS: In this study, we detect the expression of miR-34a and miR-206 in the cervical cancer tissue through quantificational real-time polymerase chain reaction (qRT-PCR) assay, and the expression of Bcl2 and c-Met from cervical cancer tissue were detected by immunohistochemistry. RESULTS: The expression of miR-34a and miR-206 were down-regulated in the cervical cancer tissue through qRT-PCR assay. As target genes of miR-34a and miR-206, Bcl2 and c-Met were up-regulated in cervical cancer tissues through qRT-PCR assay and immunohistochemistry. Kaplan-Meier and log-rank analysis revealed that down-regulated expression of miR-34a and miR-206 were strongly related to shorter overall survival. Multivariate Cox proportional hazards model for all variables that were statistically significant in the univariate analysis demonstrated that miR-34a (P = 0.038) and miR-206 (P = 0.008) might be independent prognostic factors for overall survival of patients suffering from cervical cancer. CONCLUSIONS: The up-regulation of Bcl2 and c-Met promotes the cervical cancer's progress, and the expression of miR-34a and miR-206 significantly correlated with the progression and prognosis in cervical cancer. All of these suggested that miR-34a and miR-206 might be the novel prognostic and therapy tools in cervical cancer.

Hemoglobin A1c and risk of left atrial thrombus and spontaneous echo contrast in non-valvular atrial fibrillation patients.

OBJECTIVES: To evaluate the relationship between hemoglobin A1c (HbA1c) and risk of left atrial thrombus/spontaneous echo contrast (LAT/SEC) in non-valvular atrial fibrillation (AF) patients. METHODS: In this retrospective study, 1158 consecutive non-valvular AF patients undergoing transesophageal echocardiography prior to radiofrequency catheter ablation or electric cardioversion were enrolled. Baseline characteristics were collected and analyzed. RESULTS: There were 87 (7.5%) patients with LAT/SEC. The HbA1c levels in the patients with LAT/SEC were significantly higher than that in patients without LAT/SEC (6.13 ± 0.41 vs. 5.89 ± 0.45 µmol/L, P < 0.001). The optimal cut-off point for HbA1c predicting LAT/SEC was 6.1% determined by receiver-operating characteristic curve. The area under the curve is 0.788 (95% confidence interval: 0.764-0.812). HbA1c ≥6.1% was an independent risk factor for LAT/SEC (odds ratio, 1.74; 95% confidence interval, 1.01-2.98; P = 0.045). CONCLUSIONS: Elevated HbA1c indicated a significantly increased risk for LAT/SEC in non-valvular AF patients. HbA1c might have significance in predicting the risk for prothrombotic state in non-valvular AF patients.

Hydrogen sulfide inhibits MPP+-induced aldehyde stress and endoplasmic reticulum stress in PC12 cells: involving upregulation of BDNF.

We have previously demonstrated the protective action of hydrogen sulfide (H2S) in 1-Methy-4-Phenylpyridinium Ion (MPP+)-induced neurotoxicity. However, the exact mechanisms of this protection remain largely unknown. Aldehyde stress and endoplasmic reticulum (ER) stress play significant roles in the neurotoxicity of MPP+. Brain derived neurotrophic factor (BDNF) is an important endogenous neuroprotectant. Therefore, we speculated that the protection of H2S against MPP+ neurotoxicity results from inhibiting MPP+-induced aldehyde stress and ER stress via upregulation of BDNF. In the present study, we found that NaHS, a donor of H2S, inhibited MPP+-induced aldehyde stress (the accumulations of the intracellular 4-HNE and MDA) and ER stress (the increases in the expressions of GRP78 and Cleaved-caspase-12) in PC12 cells and upregulated the BDNF expression in MPP+-exposed PC12 cells. Furthermore, we found that pretreatment of PC12 cells with K252a, an inhibitor of the BDNF receptor TrkB, not only markedly reversed the inhibitiory role of NaHS in MPP+-induced aldehyde stress and ER stress, but also ablated the protection of NaHS against MPP+-induced neurotoxicity. These data demonstrated that the protective role of H2S against MPP+-induced neurotoxicity by inhibiting aldehyde stress and ER stress, which is involved in upregulation of BDNF.

Sulforaphane prevents rat cardiomyocytes from hypoxia/reoxygenation injury in vitro via activating SIRT1 and subsequently inhibiting ER stress.

AIM: Sulforaphane (SFN), a natural dietary isothiocyanate, is found to exert beneficial effects for cardiovascular diseases. This study aimed to investigate the mechanisms underlying the protective effects of SFN in a model of myocardial hypoxia/reoxygenation (H/R) injury in vitro. METHODS: Cultured neonatal rat cardiomyocytes pretreated with SFN were subjected to 3-h hypoxia followed by 3-h reoxygenation. Cell viability and apoptosis were detected. Caspase-3 activity and mitochondrial membrane potential (ΔΨm) was measured. The expression of ER stress-related apoptotic proteins were analyzed with Western blot analyses. Silent information regulator 1 (SIRT1) activity was determined with SIRT1 deacetylase fluorometric assay kit. RESULTS: SFN (0.1-5 µmol/L) dose-dependently improved the viability of cardiomyocytes, diminished apoptotic cells and suppressed caspase-3 activity. Meanwhile, SFN significantly alleviated the damage of ΔΨm and decreased the expression of ER stress-related apoptosis proteins (GRP78, CHOP and caspase-12), elevating the expression of SIRT1 and Bcl-2/Bax ratio in the cardiomyocytes. Co-treatment of the cardiomyocytes with the SIRT1-specific inhibitor Ex-527 (1 µmol/L) blocked the SFN-induced cardioprotective effects. CONCLUSION: SFN prevents cardiomyocytes from H/R injury in vitro most likely via activating SIRT1 pathway and subsequently inhibiting the ER stress-dependent apoptosis.

[Changes in serum level of carboxy-terminal telopeptide of type I collagen in patients with coronary heart disease].

OBJECTIVE: To investigate the serum level of carboxy-terminal telopeptide of type I collagen (ICTP) and explore its correlation with MMP-2 and MMP-9 in patients with coronary artery disease (CHD). METHODS: A total of 103 CHD patients treated in our hospital between October, 2013 and May, 2014 were enrolled, including 39 with stable angina pectoris (SAP), 39 with unstable angina (UA), and 25 with acute myocardial infarction (AMI), with 38 non-CHD volunteers as the control group. The serum levels of ICTP, MMP-2, and MMP-9 were detected in all the subjects using enzyme-linked immunosorbent assay (ELISA). RESULTS: No significant difference in serum levels of MMP-2, MMP-9, or ICTP was found between the control and SAP groups or between UA and AMI groups (P>0.05), but the latter two groups had significantly higher serum levels of MMP-2, MMP-9, and ICTP than the former two groups (P<0.05). Serum ICTP level was found to negatively correlated with the fibrotic area and positively with the lipid component in the plaques (P<0.05). Regression analysis revealed significant positive correlations of serum ICTP with MMP-2 and MMP-9 (P<0.05). CONCLUSION: An elevated serum ICTP level is indicative of the presence of unstable plaques in CHD patients. Serum ICTP is more strongly correlated with MMP-2 than with MMP-9, and can be used as a non-invasive marker for assessing vulnerable plaques in patients with acute coronary syndrome.

Serum dehydroepiandrosterone sulfate concentration is lower in women with primary aldosteronism.

OBJECTIVE: The objective of this article is to measure serum dehydroepiandrosterone sulfate (DHEA-S) concentration in both genders with primary aldosteronism (PA). MATERIALS AND METHODS: The study enrolled 78 subjects with normal controls, 46 subjects with essential hypertension and 85 subjects with PA from October 2007 to June 2011. Subjects with PA were divided into three subtype groups: aldosterone-producing adenoma (APA), bilateral idiopathic hyperplasia (IHA) and PA with negative imaging findings. RESULTS: Women with PA (n = 49) had lower serum DHEA-S levels compared with normal controls and subjects with essential hypertension (p < 0.01). In subtype analysis, only female APAs had lower serum DHEA-S levels (p < 0.01 compared with normal controls, p < 0.01 compared with subjects with essential hypertension). In APA, a significant correlation between tumor size and serum DHEA-S was found in women (p < 0.01). CONCLUSION: Our data suggested that serum DHEA-S levels are lower in women with PA. In subtype groups, only women with APA had lower serum DHEA-S. There was no significant difference between subjects with bilateral essential hyperplasia, PA with negative imaging findings, normal controls and subjects with essential hypertension in both genders. The serum DHEA-S level is negatively correlated with the size of APA.

Role of aldehyde dehydrogenase 2 in 1-methy-4-phenylpyridinium ion-induced aldehyde stress and cytotoxicity in PC12 cells.

Aldehyde stress contributes to molecular mechanisms of cell death and the pathogenesis of Parkinson's disease (PD). The neurotoxin 1-Methy-4-Phenylpyridinium Ion (MPP(+)) is commonly used to model PD. Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme detoxifying aldehydes. The aim of this study is to evaluate whether MPP(+)-induced neurotoxicity is involved in aldehyde stress by modulation of ALDH2. Our results demonstrated that treatment of PC12 cells with MPP(+) leads to aldehyde stress by increasing in loads of malondialdehyde and 4-hydroxynonenal, which indicated that MPP(+)-induced aldehyde stress contributes to its cytotoxicity in PC12 cells. We also showed that MPP(+) up-regulates the expression and activity of ALDH2 in PC12 cells and that inhibition of ALDH2 by its specific inhibitor daidzin prevents MPP(+)-induced decrease in cell viability and increases in apoptosis, oxidative stress and aldehyde stress in PC12 cells. These findings suggest that aldehyde stress contributes to MPP(+)-induced toxicity in PC12 cells by upregulation of ALDH2. This study provides a novel insight into the role of ALDH2 in the neurotoxicity of MPP(+).

[Meta-analysis on the prognostic value of pregnancy-associated plasma protein-A in acute coronary syndrome].

OBJECTIVE: To evaluate the overall prognostic effects of pregnancy-associated plasma protein-A (PAPP-A) in acute coronary syndrome (ACS) through a meta-analysis. METHODS: Literature was retrieved by formal searching of electronic databases (PubMed, EMBASE, OVID, Web of Knowledge, and the Cochrane Library) and by hand searching of reference lists of related articles. Random effects meta-analysis and relative risk were used to estimate the association between PAPP-A levels and adverse cardiovascular outcomes after ACS as well as preplanned subgroup analyses were conducted to identify the risk-subgroup interactions that could explain the between differences. RESULTS: A total of fourteen clinical trials were included in this Meta-analysis which involving 9413 patients. Pooled RR and their 95% confidence intervals (CIs) for all eligible studies was 1.97 (1.49 - 2.60), which indicated a prognostic value of PAPP-A in patients with ACS. Differences in study design, measurement of association and duration of follow-up were responsible for the differences in results across the studies. CONCLUSION: Our results suggested that a higher early blood PAPP-A could moderately increase the long-term risk of adverse cardiovascular outcomes and might serve as a valuable prognostic predictor in patients with ACS.

The role of triglyceride in cardiovascular disease in asian patients with type 2 diabetes--a systematic review.

In Asian populations, diabetes mellitus is increasing and has become an important health problem in recent decades. Cardiovascular disease (CVD) is one of the most important complications and the most common cause of death in diabetic patients. Among the risk factors of CVD, elevated low-density lipoprotein cholesterol has been a major concern. Studies suggested that serum triglyceride may also play a role in predicting CVD in patients with type 2 diabetes mellitus, but the association is still debated. In this review, we summarized published studies focusing on the relationship between serum triglyceride and CVD disease in Asian diabetic patients. Ten studies conducted in six different Asian countries (three from Hong Kong, two from Taiwan, tow from Japan, one from Indonesia, one from South India, and one from South Korea) were summarized and discussed. CVD was subdivided into coronary heart disease, stroke, and peripheral arterial disease. Of the ten studies analyzed, one focused on CVD, five on coronary heart disease, three on stroke, three on peripheral arterial disease, and one on mortality from CVD. Studies from Hong Kong, Taiwan, and Japan suggested that triglyceride is a significant and independent risk factor for coronary heart disease, but not a significant risk factor for stroke (studies conducted in Japan and South Korea) or peripheral arterial disease (studies conducted in Taiwan, Indonesia, and South India). Although serum triglyceride may be a significant risk factor for coronary heart disease in Asian diabetic patients, clinical trials evaluating whether lowering triglycerides using fibrates can reduce the risk of coronary heart disease in these patients need to be initiated.

Suppression of rat Frizzled-2 attenuates hypoxia/reoxygenation-induced Ca2+ accumulation in rat H9c2 cells.

Growing evidence suggests that Ca(2+) overload is one of the major contributors of myocardial ischemia/reperfusion-induced injury. Since Frizzled-2 receptor, a seven transmembrane protein, transduces downstream signaling by specialized binding of Wnt5a to increase intracellular Ca(2+) release, this work aimed to investigate the effect of Frizzled-2 on Ca(2+) accumulation in H9c2 cells, which were subjected to hypoxia/reoxygenation to mimic myocardial ischemia/reperfusion. After exposing H9c2 cells to hypoxia/reoxygenation, we observed higher expression of Frizzled-2 and Wnt5a as compared to control group cells. Hypoxia/reoxygenation-induced intracellular Ca(2+) accumulation approached that of cells transfected with frizzled-2 plasmid. In cells treated with RNAi specifically designed against frizzled-2, intracellular Ca(2+) in both hypoxia/reoxygenation-treated cells and plasmid-treated cells were decreased. Rats that underwent ischemia/reperfusion injury exhibited increased intracellular Ca(2+) with high expression levels of Frizzled-2 and Wnt5a as compared to the sham group. Our data indicates that upon binding to Wnt5a, increased Frizzled-2 expression after hypoxia/reoxygenation treatment activated intracellular calcium release in H9c2 cells. Our findings provide a new perspective in understanding calcium overload in myocardial ischemia/reperfusion.

[Echo-tracking technology for evaluating the impact of blood pressure on vascular endothelial function].

OBJECTIVE: To evaluate the effect of blood pressure on vascular endothelial function using echo-tracking (ET) technology. METHODS: Thirty hypertensive (HP) patients, 30 subjects with high normal blood pressure (HN), and 30 normotensive control (NC) subjects were enrolled in this study. For each subject, conventional two-dimensional ultrasound was performed to measure the intima-media thickness (IMT), and an ET system was utilized to assess the carotid elasticity (Ep, ß, AC, AI, and PWVß). RESULTS: As the blood pressure increased, IMT, Ep, ß, AI, and PWVß values all increased and AC value decreased. Before excluding the confounding factors, the difference in IMT, Ep, ß, AC, AI, and PWVß values were significant between the 3 groups. After excluding the confounding factors, only PWVß value was significantly different between HN group and NC group; but between HP and NC group and between HP and HN group, the other parameters still showed significant differences. Systolic blood pressure had significant influences on IMT, Ep, AC, AI, and PWVß values, diastolic blood pressure significantly affected AI value, and pulse pressure significantly affected Ep and ß values. CONCLUSION: High normal blood pressure has no obvious effects on vascular function, and blood pressure is an independent risk factor of vascular endothelial dysfunction only in the stage of early hypertention. In early atherosclerosis, systolic blood pressure is the most significant factors affecting vascular endothelial function, followed by pulse pressure and diastolic blood pressure.

[A comparative study of target vessel assessments by three- and two-dimensional quantitative coronary X-ray angiography and visual estimation].

OBJECTIVE: To compare the efficacy of three-dimensional (3D) and two-dimensional (2D) quantitative coronary X-ray angiography (QCA) and visual estimation in the assessment of target vessels. METHODS: The radiographic data of 60 patients (65 vessel segments) receiving coronary angiography and interventional stent placement were retrospectively analyzed. The area stenosis, diameter stenosis, lesion length, and reference diameter assessed by Medis 3D QCA, Siemens 2D QCA and visual estimation were compared. RESULTS: Three-dimensional reconstruction was successfully performed for 65 vessel segments, and 3 target vessel were excluded due to the lack of a second angiographic view for 3D reconstruction. There were significant differences in the assessments of the area stenosis [(73.87 ∓ 8.98)% vs (79.10 ∓ 8.06)% vs (83.53 ∓ 8.19)%, P<0.001], lesion length (28.95 ∓ 17.31 mm vs 26.20 ∓ 16.04 mm vs 27.21 ∓ 16.58 mm, P<0.001), reference diameter (28.95 ∓ 17.31 mm vs 26.2 ∓ 16.04 mm vs 27.21∓16.58 mm, P<0.001) by 3D QCA, 2D QCA and visual estimation; the diameter stenosis assessed by 3D [(54.21 ∓ 9.48)%] and 2D QCA [(57.84 ∓ 10.17)%] also differed significantly (P=0.016). CONCLUSION: 3D QCA allows successful three-dimensional reconstruction of the target vessel and restores the actual dimensions of the vessel for a more accurate assessment of coronary artery disease than 2D QCA and visual estimation.