Liraglutide Attenuates Aortic Valve Calcification in a High-Cholesterol-Diet-Induced Experimental Calcific Aortic Valve Disease Model in Apolipoprotein E-Deficient Mice.

BACKGROUND: Calcific aortic valve disease (CAVD) is a significant cause of morbidity and mortality among elderly people. However, no effective medications have been approved to slow or prevent the progression of CAVD. Here, we examined the effect of liraglutide on aortic valve stenosis. METHODS: Male Apoe-/- mice were fed with a high-cholesterol diet for 24 weeks to generate an experimental CAVD model and randomly assigned to a liraglutide treatment group or control group. Echocardiography and immunohistological analyses were performed to examine the aortic valve function and morphology, fibrosis, and calcium deposition. Plasma Glucagon-like peptide-1 (GLP-1) levels and inflammatory contents were measured via ELISA, FACS, and immunofluorescence. RNA sequencing (RNA-seq) was used to identify liraglutide-affected pathways and processes. RESULTS: Plasma GLP-1 levels were reduced in the CAVD model, and liraglutide treatment significantly improved aortic valve calcification and functions and attenuated inflammation. RNA-seq showed that liraglutide affects multiple myofibroblastic and osteogenic differentiations or inflammation-associated biological states or processes in the aortic valve. Those liraglutide-mediated beneficial effects were associated with increased GLP-1 receptor (GLP-1R) expression. CONCLUSIONS: Liraglutide blocks aortic valve calcification and may serve as a potential therapeutic drug for CAVD treatment.

Neutrophil to high-density lipoprotein cholesterol ratio as the risk mark in patients with type 2 diabetes combined with acute coronary syndrome: a cross-sectional study.

Chronic inflammation and dyslipidemia are important risk factors in developing atherosclerotic cardiovascular disease, such as coronary heart disease. Acute coronary syndrome (ACS) is one of the most dangerous syndromes in coronary heart disease. Type 2 diabetes mellitus (T2DM) is considered equal to coronary heart disease owing to the high cardiac risk induced by chronic inflammation and dyslipidemia. The neutrophil to high-density lipoprotein cholesterol ratio (NHR) is a novel and straightforward marker that reflects inflammation and lipid metabolic disorder. However, few studies have been on the role of NHR in assessing the risk of ACS in T2DM patients. Here we analyzed NHR level in ACS patients with T2DM, exploring its predictive and diagnostic values. 211 hospitalized ACS patients with T2DM were recruited as the case group, and 168 hospitalized T2DM patients as the control group (all patients collected from 6/2020 to 12/2021 in Xiangya Hospital). Biochemical test results and echocardiograms, as well as demographic information such as age, BMI, diabetes mellitus, smoking, drinking, and history of hypertension, were recorded. Frequencies, percentages, means, and standard deviations were used to describe the data. The shapiro-Wilk test was used to assess the normality of the data. Normally distributed data were compared using the independent sample T-test, and non-normally distributed data were compared using Mann-Whitney U test. Correlation analysis was performed using the Spearman rank correlation test, and receiver operating characteristic (ROC) curve analysis and multivariable logistic regression analysis were performed by SPSS version 24.0 (SPSS Inc) and GraphPad Prism 9.0 (GraphPad Software Inc). p < 0.05 was considered significant. In the study population, NHR was higher in patients with T2DM combined with ACS than in T2DM patients without ACS (p < 0.001). After adjusting for BMI, alcohol consumption, and history of hypertension, multifactorial logistic regression analysis revealed that NHR is a risk factor for T2DM patients combined with ACS (OR 1.221, p = 0.0126). Correlation analysis on all ACS patients with T2DM showed that NHR level was positively correlated with cTnI (r = 0.437, p < 0.001), CK (r = 0.258, p = 0.001), CK-Mb (r = 0.447, p < 0.001), LDH (r = 384, p < 0.001), Mb (r = 0.320, p < 0.001), LA (r = 0.168, p = 0.042) and LV levels (r = 0.283, p = 0.001). And meanwhile, NHR level was negatively correlated with EF (r = - 0.327, p < 0.001) and FS levels (r = - 0.347, p < 0.001). ROC curve analysis showed that NHR ≧ 4.32 had a sensitivity of 65.45% and a specificity of 66.19% for predicting ACS in T2DM patients [area under the curve (AUC) = 0.722, p < 0.001]. Furthermore, in all ACS patients with T2DM, the diagnostic power of NHR was stronger in ST-segment elevated ACS patients (STE-ACS) than that in non-ST-segment elevated ACS patients (NSTE-ACS) (p < 0.001). With its convenience and effective character, NHR could be a potential and new marker for predicting the presence, progression, and severity of ACS in T2DM population.

The mir-21 Inhibition Enhanced HUVEC Cellular Viability during Hypoxia-Reoxygenation Injury by Regulating PDCD4.

The purpose of this study was to explore the clinical value of altered plasma mir-21 expression level as a biomarker for the severity of coronary artery disease (CAD) and its molecular impact on HUVEC cellular injuries. Angiographically validated 56 patients with single-vessel CAD disease, 92 patients with double-vessel CAD, 139 complex coronary artery stenosis patients, and 56 healthy individuals (n = 343) were enrolled in this study. The expressions of plasma mir-21 were evidently and progressively higher while PDCD4 levels were significantly and steadily lower in single-, dual-, and multivessel occluded CAD patients than in healthy participants (P < 0.001). The relative expressions of mir-21 in hypoxia-reoxygenation- (HR-) exposed HUVECs were markedly upregulated, but PDCD4 concentrations were obviously downregulated as compared with normal control cells (P < 0.001). Moreover, altered circulatory mir-21 expression levels were able to significantly differentiate single- (AUC 0.893), double- (AUC 0.914), and multivessel stenosis CAD (AUC 0.933) patients from healthy subjects. Besides, the plasma mir-21 expressions in elderly (66-85 years) groups were remarkably higher than those in younger aged (25-45 years) subjects. Caspase-3 and ROS expression levels were remarkably elevated, but cellular viability noticeably declined in HR-induced HUVECs than in normoxic cells (P < 0.001). In contrast, mir-21 inhibition markedly reduced caspase-3 activity and ROS concentrations while significantly ameliorating HUVEC cellular viability in HR conditions. PDCD4 expressions in HR-exposed HUVECs were prominently decreased whereas mir-21 inhibition significantly enhanced PDCD4 levels (P < 0.001). Upregulated plasma mir-21 can be a valuable clinical biomarker for the detection of the severity of coronary artery stenosis patients. Elevated circulatory mir-21 concentrations have a positive correlation with aging. Inhibitory mir-21 evidently increased HUVEC cellular viability through upregulation of targeting PDCD4 and recommended a newer possible therapeutic molecule for the management of CAD patients.

miR-129 Attenuates Myocardial Ischemia Reperfusion Injury by Regulating the Expression of PTEN in Rats.

PTEN/AKT signaling plays pivotal role in myocardial ischemia reperfusion injury (MIRI), and miRNAs are involved in the regulation of AKT signaling. This study was designed to investigate the interaction between miR-129 and PTEN in MIRI. A MIRI rat model and a hypoxia reoxygenation (H/R) H9C2 cell model were constructed to simulate myocardial infarction clinically. TTC staining, creatine kinase (CK) activity, TUNEL/Hoechst double staining, Hoechst staining and flow cytometer were used for evaluating myocardial infarction or cell apoptosis. miR-129 mimic transfection experiment and luciferase reporter gene assay were conducted for investigating the function of miR-129 and the interaction between miR-129 and PTEN, respectively. Real-time PCR and western blotting were performed to analyze the gene expression. Compared to the control, MIRI rats presented obvious myocardial infarction, higher CK activity, increased expression of caspase-3 and PTEN, decreased expression of miR-129, and insufficient AKT phosphorylation. Consistently, H/R significantly increased the apoptosis of H9C2 cells, concomitant with the downregulation of miR-129, upregulation of PTEN and caspase-3, and insufficient phosphorylation of AKT, while miR-129 mimic obviously inhibited the expression of PTEN and caspase-3, increased the AKT phosphorylation, and decreased the cell apoptosis. Additionally, miR-129 mimic obviously decreased the relative luciferase activity in H9C2 cells. To our best knowledge, this study firstly found that the low expression of miR-129 accelerates the myocardial cell apoptosis by directly targeting 3'UTR of PTEN. miR-129 is an important biomarker for MIRI, as well as a potential therapy target.

Therapeutic Value of miRNAs in Coronary Artery Disease.

Atherosclerotic ischemic coronary artery disease (CAD) is a significant community health challenge and the principal cause of morbidity and mortality in both developed and developing countries for all ethnic groups. The progressive chronic coronary atherosclerosis is the main underlying cause of CAD. Although enormous progress occurred in the last three decades in the management of cardiovascular diseases, the prevalence of CAD continues to increase worldwide, indicating the need for discovery of deeper molecular insights of CAD mechanisms, biomarkers, and innovative therapeutic targets. Recently, several research groups established that microRNAs essentially regulate various cardiovascular development and functions, and a deregulated cardiac enriched microRNA profile plays a vital role in the pathogenesis of CAD and its biological aging. Numerous studies established that over- or downregulation of a single miRNA gene by ago-miRNA or anti-miRNA is enough to modify the CAD disease process, significantly prevent age-dependent cardiac cell death, and markedly improve cardiac function. In the light of more recent experimental and clinical evidences, we briefly reviewed and discussed the involvement of miRNAs in CAD and their possible diagnostic/therapeutic values. Moreover, we also focused on the role of miRNAs in the initiation and progression of the atherosclerosis plaque as the strongest risk factor for CAD.

Effect of oxymatrine on liver gluconeogenesis is associated with the regulation of PEPCK and G6Pase expression and AKT phosphorylation.

An increase in liver gluconeogenesis is an important pathological phenomenon in type 2 diabetes mellitus (T2DM) and oxymatrine is an effective natural drug used for T2DM treatment. The present study aimed to explore the effect of oxymatrine on gluconeogenesis and elucidate the underlying mechanism. Male Sprague-Dawley rats were treated with a high-fat diet and streptozotocin for 4 weeks to induce T2DM, and HepG2 cells were treated with 55 mM glucose to simulate T2DM in vitro. T2DM rats were treated with oxymatrine (10 or 20 mg/kg weight) or metformin for 4 weeks, and HepG2 cells were treated with oxymatrine (0.1 or 1 µM), metformin (0.1 µM), or oxymatrine combined with MK-2206 (AKT inhibitor) for 24 h. Fasting blood glucose and insulin sensitivity of rats were measured to evaluate insulin resistance. Glucose production and uptake ability were measured to evaluate gluconeogenesis in HepG2 cells, and the expression of related genes was detected to explore the molecular mechanism. Additionally, the body weight, liver weight and liver index were measured and hematoxylin and eosin staining was performed to evaluate the effects of the disease. The fasting glucose levels of T2DM rats was 16.5 mmol/l, whereas in the control rats, it was 6.1 mmol/l. Decreased insulin sensitivity (K-value, 0.2), body weight loss (weight, 300 g), liver weight gain, liver index increase (value, 48) and morphological changes were observed in T2DM rats, accompanied by reduced AKT phosphorylation, and upregulated expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). High-glucose treatment significantly increased glucose production and decreased glucose uptake in HepG2 cells, concomitant with a decrease in AKT phosphorylation and increase of PEPCK and G6Pase expression. In vivo, oxymatrine dose-dependently increased the sensitivity of T2DM rats to insulin, increased AKT phosphorylation and decreased PEPCK and G6Pase expression in the liver, and reversed the liver morphological changes. In vitro, oxymatrine dose-dependently increased AKT phosphorylation and glucose uptake of HepG2 cells subjected to high-glucose treatment, which was accompanied by inhibition of the expression of the gluconeogenesis-related genes, PEPCK and G6Pase. MK-2206 significantly inhibited the protective effects of oxymatrine in high-glucose-treated cells. These data indicated that oxymatrine can effectively prevent insulin resistance and gluconeogenesis, and its mechanism may be at least partly associated with the regulation of PEPCK and G6Pase expression and AKT phosphorylation in the liver.

Combination of ponatinib with deferoxamine synergistically mitigates ischemic heart injury via simultaneous prevention of necroptosis and ferroptosis.

Necroptosis, ferroptosis and cyclophilin D (Cyp D)-dependent necrosis contribute to myocardial ischemia/reperfusion (I/R) injury, and ponatinib, deferoxamine and cyclosporine are reported to inhibit necroptosis, ferroptosis and Cyp D-dependent necrosis, respectively. This study aims to explore whether the any two combination between ponatinib, deferoxamine and cyclosporine exerts a better cardioprotective effect on I/R injury than single medicine does. The H9c2 cells were subjected to 10 h of hypoxia (H) plus 4 h of reoxygenation (R) to establish H/R injury model. The effects of any two combination between ponatinib, deferoxamine and cyclosporine on H/R injury were examined. On this basis, a I/R injury model in rat hearts was established to focus on the effect of ponatinib, deferoxamine and their combination on myocardial I/R injury and the underlying mechanisms. In H/R-treated H9c2 cells, all three medicines can attenuate H/R injury (decrease in LDH release and necrosis percent). However, only the combination of ponatinib with deferoxamine exerted synergistic effect on reducing H/R injury, showing simultaneous suppression of necroptosis and ferroptosis. Expectedly, administration of ponatinib or deferoxamine either before or after ischemia could suppress necroptosis or ferroptosis in the I/R-treated rat hearts as they did in vitro, concomitant with a decrease in myocardial infarct size and creatine kinase release, and the combination therapy is more efficient than single medication. Based on these observations, we conclude that the combination of ponatinib with deferoxamine reduces myocardial I/R injury via simultaneous inhibition of necroptosis and ferroptosis.

Diagnostic Role of Plasma MicroRNA-21 in Stable and Unstable Angina Patients and Association with Aging.

The present study explored the clinical value of plasma microRNA-21 as a novel biomarker for early prediction of stable and unstable angina patients and its relationship with aging. A total of 255 participants, 123 patients with chronic stable angina, 82 patients with unstable angina, and 50 healthy subjects, were included in our study. Stable coronary and unstable coronary patients were confirmed following AHA/ACC clinical protocols. Total RNA was extracted from plasma by using miRNA-based TRIzol reagent. Plasma miR-21 expression levels were determined by real-time polymerase chain reaction. To evaluate the diagnosis accuracy, the receiver operating characteristic (ROC) curves were used. Plasma microRNA-21 concentration levels were significantly elevated in stable and unstable angina patients as compared with control subjects (P < 0.001). The area under the ROC curves of circulating microRNA-21 was accurately distinguished in stable angina patients (AUC 0.921) and unstable angina patients (AUC 0.944) from healthy subjects. MicroRNA-21 expression gradually elevated with increasing aging in all the populations. Moreover, the current study also demonstrated that the expression of plasma miR-21 levels was significantly associated with different age groups within healthy subjects and stable and unstable angina patients (P < 0.001). This research finding suggested that plasma microRNA-21 may be considered as a suitable new biomarker for early detection of stable and unstable angina patients, and it has a strong correlation with aging.

Overexpression of miR-375 Protects Cardiomyocyte Injury following Hypoxic-Reoxygenation Injury.

The aim of the study was to evaluate the clinical significance of microRNA-375 in acute myocardial infarction patients and its mimic action in hypoxia/reoxygenation- (H/R-) induced ventricular cardiomyocyte H9c2 injury. In the current study, 90 ST-elevated acute MI patients (STEMI), 75 non-ST-elevated acute MI patients (NSTEMI), 90 healthy subjects, 14 weeks old mice, and ventricular cardiomyocyte H9c2 were included. The expressions of plasma microRNA-375 in patients with STEMI and NSTEMI and AMI mouse models were remarkably decreased than in controls (P < 0.001). The areas under the curve (AUC) of plasma microRNA-375 were revealed 0.939 in STEMI and 0.935 in NSTEMI subjects. Moreover, microRNA-375 levels in H/R-exposed cardiac H9c2 cells were evidently downregulated and significantly increased apoptosis rate and caspase-3 activity levels, while overexpression of miR-375 remarkably reduced apoptosis percentage and caspase-3 levels as compared with normal cells. Furthermore, this study also demonstrated that Nemo-like kinase (NLK), NLK mRNA, and protein expression levels were significantly downregulated in H/R-injured H9c2 cells, on the contrary, H9c2 cells transfected with mimic-miR-375 greatly upregulated NLK mRNA and protein expression. Plasma microRNA-375 may serve as an essential clinical biomarker for diagnosis of early-stage AMI. Mimic expression of miR-375 significantly prevented H/R-induced cardiomyocyte injury by decreasing caspase-3 activity through upregulation of the NLK gene, recommended as a new therapeutic option for AMI patient.

Current Status of Knowledge about Cardiopulmonary Resuscitation among the University Students in the Northern Region of Saudi Arabia.

BACKGROUND: Sudden cardiac arrest is a major public health problem in the world. Immediate initiation of high-quality cardiopulmonary resuscitation (CPR) significantly increased patient survival rate. Therefore, it is very important to train young people and increase public awareness of CPR for the long-term benefit of the community. OBJECTIVE: We aimed at estimating the level of knowledge and attitude towards cardiopulmonary resuscitation (CPR) among the university students in the northern region of Saudi Arabia. METHODOLOGY: A cross-sectional, prospective study was conducted among the students of four northern region universities of Saudi Arabia (Jouf, Hail, Northern Borders, and Tabuk) between March and November 2017. A self-administered questionnaire was prepared in both Arabic and English languages and distributed to all the participants. All the data were collected and analyzed by using SPSS version 21. RESULTS: A total of 947 students from four universities completed the questionnaire: Jouf (57%), Hail (15%), Northern Borders (13%), and Tabuk (15%). Although 72% of students have previous knowledge about CPR, 49% of them lack knowledge about a medical emergency. Moreover, 59% failed to answer regarding CPR where only 41% wrote the ABC steps in the correct sequence. However, 67% of the participants had very poor knowledge, 89% of participants desired to receive additional CPR training course, and 49% of the students thought that CPR training should be a mandatory graduation requirement for all universities. There were no significant differences between male and female students. Students from medicine-related colleges have significantly (p < 0.001) more knowledge and scored better compared with non-medicine-related colleges. Tabuk University scored better compared to the others, but the overall knowledge and attitude scored were low. CONCLUSIONS: Overall knowledge about CPR among the university students was not satisfactory; however, attitude towards CRP training was very positive. Our results suggested that there is a need for improvement of CPR education among Saudi university students, which will help to reduce the cardiac arrest mortality rate among the community.

Protective Effects of α-Boswellic Acids in a Pulmonary Arterial Hypertensive Rat Model.

The purpose of this study was to observe the protective effects of α-boswellic acids on hypoxia-induced pulmonary vascular structural remodeling in pulmonary arterial smooth muscle cells in a hypertensive rat model. Pulmonary arterial smooth muscle cells were cultured and then randomly divided into four groups: normoxia, hypoxia (3 % O2; 24 h), hypoxia plus α-boswellic acids, and hypoxia plus DMSO (as a positive control), according to the different concentrations of α-boswellic acids (21.90 µM, 43.79 µM, and 87.58 µM). Apoptosis and proliferation of pulmonary arterial smooth muscle cells significantly decreased in the hypoxia plus α-boswellic acids group compared with the hypoxia and hypoxia plus DMSO groups (n = 8, p < 0.05). The mRNA and protein phosphorylation levels of c-Jun N-terminal kinase 1 and extracellular regulated protein kinase 1 were significantly elevated in hypoxic cells compared with normal cells. However, the mRNA and protein phosphorylation levels of c-Jun N-terminal kinase 1 and extracellular regulated protein kinase 1 markedly decreased in the hypoxia plus α-boswellic acids group compared with the hypoxia plus DMSO group (n = 8, p < 0.05; n = 13, p < 0.05, respectively). Our findings suggest that α-boswellic acids can inhibit inappropriate apoptosis and excessive proliferation of pulmonary arterial smooth muscle cells and pulmonary vascular remodeling by repressing the expression of c-Jun N-terminal kinase 1 and extracellular regulated protein kinase 1 under hypoxic conditions.

Diagnostic, Prognostic, and Therapeutic Value of Circulating miRNAs in Heart Failure Patients Associated with Oxidative Stress.

Heart failure is a major public health problem especially in the aging population (≥65 years old), affecting nearly 5 million Americans and 15 million European people. Effective management of heart failure (HF) depends on a correct and rapid diagnosis. Presently, BNP (brain natriuretic peptide) or N-terminal pro-brain natriuretic peptide (NT-proBNP) assay is generally accepted by the international community for diagnostic evaluation and risk stratification of patients with HF. However, regardless of its widespread clinical use, BNP is still encumbered by reduced specificity. As a result, diagnosis of heart failure remains challenging. Although significant improvement happened in the clinical management of HF over the last 2 decades, traditional treatments are ultimately ineffective in many patients who progress to advanced HF. Therefore, a novel diagnostic, prognostic biomarker and new therapeutic approach are required for clinical management of HF patients. Circulating miRNAs seem to be the right choice for novel noninvasive biomarkers as well as new treatment strategies for HF. In this review, we briefly discuss the diagnostic, prognostic, and therapeutic role of circulating miRNAs in heart failure patients. We also mentioned our own technique of extraction of RNA and detection of circulating miRNAs from human plasma and oxidative stress associated miRNAs with HF.

Extensive metabolic disorders are present in APC(min) tumorigenesis mice.

Wnt signaling plays essential role in mesenchymal stem cell (MSC) differentiation. Activation of Wnt signaling suppresses adipogenesis, but promotes osteogenesis in MSC. Adenomatous polyposis coli (APC) is a negative regulator of ß-catenin and Wnt signaling activity. The mutation of APC gene leads to the activation of Wnt signaling and is responsible for tumorigenesis in APC(min) mouse; however, very few studies focused on its metabolic abnormalities. The present study reports a widespread metabolic disorder phenotype in APC(min) mice. The old APC(min) mice have decreased body weight and impaired adipogenesis, but severe hyperlipidemia, which mimic the phenotypes of Familial Adenomatous Polyposis (FAP), an inherited disease also caused by APC gene mutation in human. We found that the expression of lipid metabolism and free fat acids (FA) use genes in the white adipose tissue (WAT) of the APC(min) mice is much lower than those of control. The changed gene expression pattern may lead to the disability of circulatory lipid transportation and storage at WAT. Moreover, the APC(min) mice could not maintain the core body temperature in cold condition. PET-CT determination revealed that the BAT of APC(min) mice has significantly impaired ability to take up (18)FDG from the blood. Morphological studies identified that the brown adipocytes of APC(min) mice were filled with lipid droplets but fewer mitochondria. These results matched with the findings of impaired BAT function in APC(min) mice. Collectively, our study explores a new mechanism that explains abnormal metabolism in APC(min) mice and provides insights into studying the metabolic disorders of FAP patients.

Role of Transforming Growth Factor-ß1 and Smads Signaling Pathway in Intrauterine Adhesion.

The aim of the study was to evaluate the role of Smad3, Smad7, and TGF-ß1 in intrauterine adhesion (IUA) patients and experimental rabbit models. 60 IUA patients, 30 control participants, and 18 female rabbits were enrolled in this study. We found that the plasma concentrations and protein expressions of TGF-ß1 were significantly increased in patients and experimental rabbits compared to those in controls (P < 0.05). Furthermore, the mRNA and protein expression levels of Smad3 were significantly elevated, while Smad7 level was markedly decreased in the patients and experimental rabbits compared with controls (P < 0.05). This altered ratio recommended that IUA was positively correlated to the mRNA and protein expression levels of Smad3, Smad7, and TGF-ß1 in blood and uterine tissue. Moreover, we used the specific inhibitor of Smad3 (SIS3) in experimental rabbit. SIS3 obviously reduced the mRNA and protein expression of smad3 and TGF-ß1, while it increased Smad7 expression in the treatment groups as compared with IUA rabbits (P < 0.05). Our study suggested that TGF-ß1/Smad3/smad7 is a major pathway which plays an important role in the regulation of the IUA and specific inhibitor of Smad3 (SIS3) may provide a new therapeutic strategy for IUA.

Reversion of left ventricle remodeling in spontaneously hypertensive rats by valsartan is associated with the inhibition of caspase-3, -8 and -9 activities.

The development of hypertension is closely associated with cardiac hypertrophy and apoptosis, and caspase-3, -8 and -9 are key enzymes of apoptosis. The aim of the present study was to evaluate the effects of valsartan on left ventricle hypertrophy and myocardial apoptosis in spontaneously hypertensive rats (SHRs) and to explore the mechanisms for valsartan against apoptosis. A total of 15 SHRs (16 weeks old) were randomly divided into two groups. The SHRs in the valsartan (n=8) and SHR groups (n=7) were fed with valsartan and distilled water for 8 weeks, respectively. Wistar-Kyoto rats (n=8) were the control group. At the end of the experiments, blood pressure, parameters regarding hypertrophy, apoptosis and activities of caspase-3, -8 and -9 were measured. The results showed that valsartan significantly reduced systolic blood pressure and left ventricular hypertrophy, improved left ventricular remodeling, attenuated the myocardial damage and apoptosis, and decreased the activities of caspase-3, -8 and -9 in SHRs. In conclusion, valsartan is able to reverse hypertension-induced left ventricle remodeling, which is associated with, at least in part, its inhibitory effect on myocardial apoptosis in the death receptor-mediated extrinsic, as well as the mitochondrial-mediated intrinsic pathways.

Circulating miR-765 and miR-149: potential noninvasive diagnostic biomarkers for geriatric coronary artery disease patients.

The purpose of this study was to evaluate the diagnostic value of circulating miR-765 and miR-149 as noninvasive early biomarkers for geriatric coronary artery disease (CAD) patients. A total of 69 angiographically documented CAD patients including 37 stable CAD (72.9 ± 4.2 years) and 32 unstable CAD (72.03 ± 4.3 years) and 20 healthy subjects (71.7 ± 5.2 years), matched for age, sex, smoking habit, hypertension, and diabetes, were enrolled in this study. Compared with healthy subjects, circulating miR-765 levels were increased by 2.9-fold in stable CAD and 5.8-fold in unstable CAD patients, respectively, while circulating miR-149 levels were downregulated by 3.5-fold in stable CAD and 4.2-fold in unstable CAD patients, respectively. Furthermore, plasma levels of miR-765 were found to be positively correlated with ages within control, stable, and unstable groups. The ROC curves of miR-765 and miR-149 represented significant diagnostic values with an area under curve (AUC) of 0.959, 0.972 and 0.938, 0.977 in stable CAD patients and unstable CAD patients as compared with healthy subjects, respectively. Plasma levels of miR-765 and miR-149 might be used as noninvasive biomarkers for the diagnosis of CAD in geriatric people.