Triglyceride glucose index predicts all-cause mortality in oldest-old patients with acute coronary syndrome and diabetes mellitus.

BACKGROUND: Acute coronary syndrome (ACS) and diabetes mellitus (DM) are the leading health risks for the elderly. Triglyceride-glucose (TyG) index is a novel and reliable indicator of insulin resistance (IR). This study aims to explore the relationship between the TyG index and all-cause mortality in oldest-old patients with ACS and DM. METHODS: Seven hundred twenty hospitalized patients with ACS aged ≥ 80 years were enrolled, and 699 patients signed informed consent for the study. During the follow-up period, 37 were lost to follow-up, and the follow-up rate was 94.7%. 231 ACS patients with DM were selected for the study's analyses. Kaplan-Meier curve, Cox regression model and receiver operating characteristic (ROC) curve were used to analyze the association between the TyG index and all-cause mortality. RESULTS: The mean age of participants was 81.58 ± 1.93 years, and 32.47% were women. Compared to TyG tertile 1, the Hazard Ratio (HR) [95% confidence interval (CI)] of all-cause mortality was 2.04 (1.09, 3.81) for TyG tertile 3 in the fully adjusted model. For the TyG index per standard deviation (SD) increment, the HR (95% CI) of all-cause mortality was 1.44 (1.13, 1.83). Further, the association between the TyG index and all-cause mortality was dose-response (P for trend = 0.026). ROC curve analyses indicated that the TyG index outperformed FBG and TG in the prediction of mortality risk and improved the prognostic value of the Gensini score combined with LVEF. CONCLUSION: The TyG index predicts the risk of all-cause mortality in the oldest-old ACS patients with DM.

Evaluation of the long-term prognostic ability of triglyceride-glucose index for elderly acute coronary syndrome patients: a cohort study.

BACKGROUND: With the advancement of the world population aging, more attention should be paid to the prognosis of elderly patients with acute coronary syndrome (ACS). Triglyceride-glucose (TyG) index is a reliable indicator of insulin resistance (IR) and is closely related to traditional risk factors of cardiovascular disease (CVD). However, the effect of TyG index on the prognosis of long-term adverse events in elderly ACS patients has not been reported. This study evaluated the prognostic power of TyG index in predicting adverse events in elderly ACS patients. METHODS: In this study, 662 ACS patients > 80 years old who were hospitalized from January 2006 to December 2012 were enrolled consecutively and the general clinical data and baseline blood biochemical indicators were collected. The follow-up time after discharge was 40-120 months (median, 63 months; interquartile range, 51‒74 months). In addition, the following formula was used to calculate the TyG index: Ln [fasting TG (mg/dL) × FBG (mg/dL)/2], and patients were divided into three groups according to the tertile of the TyG index. RESULTS: The mean age of the subjects was 81.87 ± 2.14 years, the proportion of females was 28.10%, and the mean TyG index was 8.76 ± 0.72. The TyG index was closely associated with the traditional risk factors of CVD. In the fully-adjusted Cox regression model, the Hazard ratio (95% CI) of all-cause mortality (in tertile 3) was 1.64 (1.06, 2.54) and major adverse cardiac event (MACE) (in tertile 3) was 1.36 (1.05, 1.95) for each SD increase in the TyG index. The subgroup analyses also confirmed the significant association of the TyG index and long-term prognosis. CONCLUSION: The TyG index is an independent predictor of long-term all-cause mortality and MACE in elderly ACS patients.

Prognostic value of quantitative flow ratio measured immediately after drug-coated balloon angioplasty for in-stent restenosis.

OBJECTIVES: This study aimed to evaluate prognostic value of quantitative flow ratio (QFR) in drug-coated balloon (DCB) angioplasty for in-stent restenosis (ISR). BACKGROUND: There is a high incidence of recurrent ISR after DCB angioplasty. QFR is a novel method for fast computation of fractional flow reserve for the target vessel based on quantitative coronary angiography (QCA) and fluid dynamics algorithms. METHODS: Patients participating in the RESTORE ISR China randomized trial were enrolled and classified into the recurrent restenosis group and the non-recurrent restenosis group. The binary classifications followed the QCA standards of ISR. Clinical and angiographic characteristics of the groups were analyzed, and the QFRs before and after lesion preparation and after final DCB angioplasty were measured and compared. RESULTS: A total of 208 patients who underwent follow-up angiography were enrolled in the study, with 226 lesions measured in total. QFR value after DCB angioplasty (odds ratio [OR] 0.88; 95% confidence interval [CI] 0.83-0.93; p < .0001 for 1 mm increase), lesion length (OR: 1.08; 95% CI: 1.01-1.15; p = .017), and vessel caliber lumen diameter (OR: 0.35; 95% CI 0.13-0.89; p = .027) were independently associated with recurrent restenosis after DCB angioplasty. The optimal QFR cut-off value was determined to be 0.90 with a sensitivity of 0.94, specificity of 0.56, and accuracy of 0.79 in predicting recurrent restenosis. CONCLUSIONS: The QFR value after DCB angioplasty is a promising predictor of DES ISR.

Melatonin attenuates myocardial ischemia-reperfusion injury via improving mitochondrial fusion/mitophagy and activating the AMPK-OPA1 signaling pathways.

Optic atrophy 1 (OPA1)-related mitochondrial fusion and mitophagy are vital to sustain mitochondrial homeostasis under stress conditions. However, no study has confirmed whether OPA1-related mitochondrial fusion/mitophagy is activated by melatonin and, consequently, attenuates cardiomyocyte death and mitochondrial stress in the setting of cardiac ischemia-reperfusion (I/R) injury. Our results indicated that OPA1, mitochondrial fusion, and mitophagy were significantly repressed by I/R injury, accompanied by infarction area expansion, heart dysfunction, myocardial inflammation, and cardiomyocyte oxidative stress. However, melatonin treatment maintained myocardial function and cardiomyocyte viability, and these effects were highly dependent on OPA1-related mitochondrial fusion/mitophagy. At the molecular level, OPA1-related mitochondrial fusion/mitophagy, which was normalized by melatonin, substantially rectified the excessive mitochondrial fission, promoted mitochondria energy metabolism, sustained mitochondrial function, and blocked cardiomyocyte caspase-9-involved mitochondrial apoptosis. However, genetic approaches with a cardiac-specific knockout of OPA1 abolished the beneficial effects of melatonin on cardiomyocyte survival and mitochondrial homeostasis in vivo and in vitro. Furthermore, we demonstrated that melatonin affected OPA1 stabilization via the AMPK signaling pathway and that blockade of AMPK repressed OPA1 expression and compromised the cardioprotective action of melatonin. Overall, our results confirm that OPA1-related mitochondrial fusion/mitophagy is actually modulated by melatonin in the setting of cardiac I/R injury. Moreover, manipulation of the AMPK-OPA1-mitochondrial fusion/mitophagy axis via melatonin may be a novel therapeutic approach to reduce cardiac I/R injury.

Development and validation of clinical risk score to predict the cardiac rupture in patients with STEMI.

BACKGROUND: Cardiac rupture (CR) is a fatal complication of ST-elevation myocardial infarction (STEMI) with poor prognosis. The aim of this study was to develop and validate practical risk score to predict the CR after STEMI. METHODS: A total of 11,234 STEMI patients from 7 centers in China were enrolled in our study, we firstly developed a simplified fast-track CR risk model from 7455 STEMI patients, and then prospectively validated the CR risk model using receiver-operating characteristic (ROC) curves by the other 3779 consecutive STEMI patients. This trial is registered with ClinicalTrials.gov, number NCT02484326. RESULTS: The incidence of CR was 2.12% (238/11,234), and the thirty-day mortality in CR patients was 86%. We developed a risk model which had 7 independent baseline clinical predictors (female sex, advanced age, anterior myocardial infarction, delayed admission, heart rate, elevated white blood cell count and anemia). The CR risk score system differentiated STEMI patients with incidence of CR ranging from 0.2% to 13%. The risk score system demonstrated good predictive value with area under the ROC of 0.78 (95% CI 0.73-0.84) in validation cohort. Primary percutaneous coronary intervention decreased the incidence of CR in high risk group (3.9% vs. 6.2%, p<0.05) and very high risk group (8.0% vs. 15.2%, p<0.05). CONCLUSIONS: A simple risk score system based on 7 baseline clinical variables could identify patients with high risk of CR, for whom appropriate treatment strategies can be implemented.

[Association between urinary microalbumin-to-creatinine ratio and brachial-ankle pulse wave velocity in hypertensive patients].

OBJECTIVE: To explore the association between urinary microalbumin-to-creatinine ratio (ACR) and brachial-ankle pulse wave velocity (baPWV) in hypertensive patients. METHODS: A total of 877 primary hypertension patients were enrolled in this trial from September 2009 to December 2012, and were randomly recruited and patients were divided into normal ACR group (ACR < 30 mg/g, n = 723), micro-albuminuria group (30 mg/g ≤ ACR < 300 mg/g, n = 136) and macro-albuminuria group (ACR ≥ 300 mg/g, n = 18). baPWV was measure by automatic pulse wave velocity measuring system. RESULTS: The baPWV values in patients of micro-albuminuria group and macro-albuminuria group were significantly higher than in the normal ACR group (all P < 0.05). The baPWV value of macro-albuminuria group was significantly higher than in the micro-albuminuria group (P < 0.05). Linear correlation analysis revealed that ACR was positively correlated with baPWV (r = 0.413, P < 0.01). Multiple linear regression analysis showed that ACR independently correlated with baPWV in patients with primary hypertension (ß = 0.29, R(2) = 0.112, P < 0.01) after adjusting for age, sex, body mass index, systolic blood pressure, diastolic blood pressure, blood glucose, total cholesterol, low density lipoprotein, high density lipoprotein and triglyceride. Using ACR < 30 mg/g and ACR ≥ 30 mg/g as dichotomous variable, binary logistic regression analysis showed that ACR ≥ 30 mg/g was also a risk factor of the ascending baPWV in primary hypertension patients (OR: 1.73, 95% CI: 1.62-2.98) after adjusting the traditional cardiovascular risk factors. CONCLUSION: ACR is positively correlated to baPWV in primary hypertension patients, and the ascending baPWV is a risk factor of early renal dysfunction in primary hypertension patients.

Correlation between comprehensive evaluation of coronary artery lesion severity and long-term clinical outcomes in Chinese octogenarians with acute coronary syndrome.

BACKGROUND: There is little known about long-term outcome data regarding acute coronary syndrome (ACS) in Chinese octogenarians (> 80 years old). Long-term outcomes of octogenarians with ACS may be associated with increased complicated coronary artery lesion severity. METHODS: We classified 536 consecutive octogenarians with ACS into four groups based on Gensini score. Survival and major adverse cardiac event (MACE) rates were calculated using the Kaplan-Meier method. Multivariate Cox regression was used to identify mortality predictors. The follow-up period was 27 (IQR15-36) months. RESULTS: The overall long-term mortality rate was 9.1% and increased from 3.0% in group 1 to 16.7% in group 4. Increasing coronary artery lesion severity was associated with increased long-term mortality and MACE rates. ROC curve analysis showed that the predictive cut-off value of Gensini score for mortality was 53. Gensini score provided significant reclassification of mortality (net reclassification index 0.195, P<0.01). Age, gender, heart rate, SBP, chronic renal failure, e-GFR, GRACE score, Gensini score, and ACS type were different between surviving and deceased patients. Notably, chronic renal failure (OR=2.55, P=0.036), GRACE score (OR=1.10, P=0.006), and Gensini score(OR=1.11, P=0.003) were the independent predictors of long-term mortality. CONCLUSIONS: Long-term mortality of octogenarians with ACS was associated with increased comprehensive coronary artery lesion severity. Gensini score was an effective parameter for evaluation of long-term mortality.

Improved heart function and cardiac remodelling following sacubitril/valsartan in acute coronary syndrome with HF.

AIMS: This study sought to assess the effect of treatment of sacubitril/valsartan (S/V) on improving cardiac function and reversing cardiac remodelling in patients with acute coronary syndrome (ACS) complicated with heart failure with reduced ejection fraction after percutaneous coronary intervention (PCI). METHODS AND RESULTS: We enrolled 275 ACS patients with reduced left ventricular ejection fraction after PCI. The patients were divided into the routine and S/V groups according to the treatment drugs. The symptoms, N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations, echocardiographic parameters [left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI)], major adverse cardiac events (MACEs), and adverse reactions were recorded at baseline and 6 months after treatment when a clinical follow-up was performed. The S/V group was further divided into prespecified subgroups including unstable angina (UA) group, non-ST-elevation myocardial infarction (NSTEMI) group, and ST-elevation myocardial infarction (STEMI) group according to the type of ACS. We analysed the changes in LVEF, LVMI, LVEDVI, LVESVI, and NT-proBNP in both groups and evaluated the correlation between the changes in the above variables (ΔLVEF, ΔLVMI, ΔLVEDVI, ΔLVESVI, and ΔNT-proBNP). Cox regression model was used to assess the independent risk factors of MACE. Prespecified subgroup analyses were also conducted. Compared with baseline, LVEF increased significantly (P < 0.05), NT-proBNP, LVMI, and LVESVI decreased significantly in both groups after 6 months (P < 0.05), and LVEDVI decreased significantly in the S/V group (P = 0.001). In the S/V group, ΔLVEF (t = -2.745, P = 0.006), ΔNT-proBNP (P = 0.009), ΔLVEDVI (t = 4.203, P = 0.001), and ΔLVESVI (t = 3.907, P = 0.001) were significantly improved than those in the routine group. In the S/V group, ΔLVEF was negatively correlated with ΔNT-proBNP (r = -0.244, P = 0.004), ΔLVMI (r = -0.190, P = 0.028), ΔLVEDVI (r = -0.173, P = 0.045), and ΔLVESVI (r = -0.261, P = 0.002). In Cox regression model analysis, ΔLVEF {hazard ratio [HR] = 0.87 [95% confidence interval (CI) 0.80-0.95], P = 0.003}, ΔLVEDVI [HR = 1.04 (95% CI 1.01-1.06), P = 0.013], and ΔLVESVI [HR = 1.04 (95% CI 1.01-1.08), P = 0.026] were independent risk factors for MACE. Subgroup analysis showed that ΔLVEF (t = 6.290, P = 0.001), ΔLVEDVI (t = 2.581, P = 0.011), and ΔNT-proBNP (P = 0.019) in the NSTEMI group were significantly improved than those in the UA group, ΔLVEDVI in the NSTEMI group was significantly better than that in the STEMI group (t = -3.365, P = 0.001), and ΔLVEF in the STEMI group was significantly better than that in the UA group (t = -3.928, P = 0.001). There was a significant difference in the survival probability without MACE among the three groups in the analysis of the Kaplan-Meier curve (P = 0.042). The incidence of MACE in the UA group was significantly higher than that in the NSTEMI group (32.4% vs. 6.3%, P = 0.004). CONCLUSIONS: The cardiac function is improved and cardiac remodelling is reversed significantly after treatment of S/V in ACS patients with reduced left ventricular ejection fraction after PCI, and the improvement is more obvious than the routine group. There is a significant negative correlation between the change in LVEF and the changes in NT-proBNP, LVMI, LVEDVI, and LVESVI. The increase of LVEF and the decrease of LVEDVI and LVESVI are protective factors to improve the prognosis. Patients with myocardial infarction and reduced left ventricular ejection fraction might benefit more from the initiation of S/V as first-line heart failure treatment after PCI.

Long-term prognostic impact of cystatin C on acute coronary syndrome octogenarians with diabetes mellitus.

OBJECTIVE: Cystatin C (Cys C) is a marker of renal dysfunction. Prior studies have shown that blood Cys C is related to the prognosis of coronary heart disease. The aim of the present study was to evaluate the long-term prognostic impact of Cys C on acute coronary syndrome (ACS) octogenarians with diabetes mellitus (DM). METHODS: We enrolled 660 consecutive ACS octogenarians who underwent coronary angiography and were classified into two groups based on diabetes. The baseline characters and Cys C level were measured on admission. Survival curve was calculated using the Kaplan-Meier method. Multivariate Cox regression was used to identify predictors of mortality and of major adverse cardiac events (MACE) rate. RESULTS: There were 223 and 398 patients in groups DM and non-DM who fulfilled the follow-up. The average follow-up period was 28 (IQR 16-38) months. Diastolic blood pressure (DBP) was lower, ratios of hypertension and chronic renal failure (CRF), fasting blood glucose, HbA1c and Cys C levels were higher in DM group than those in non-DM group (P<0.01). The cumulative survival of DM group was significantly lower than that of non-DM group in the long term (P = 0.018). All cause mortality and MACE of DM group were higher than those of non-DM group (P<0.05). The plasma Cys C concentration (OR = 3.32, 95% CI = 1.18-10.92, P = 0.023) was the uniqueness independent predictor for long-term all cause mortality. The plasma Cys C concentration (OR = 2.47, 95% CI = 1.07-7.86, P = 0.029) and Genesis score (OR = 1.01, 95% CI = 1.00-1.03, P = 0.043) were independent predictors for MACE in DM group. ROC curve analysis showed that the predictive cut-off value of Cys C for mortality of DM group was 1.605 (0.718, 0.704). CONCLUSIONS: Cys C is an independent predictor for long-term mortality and MACE of ACS octogenarians with DM.

Filterless optical oxygen sensor based on a CMOS buried double junction photodiode.

We present a custom CMOS IC with a buried double junction (BDJ) photodiode to detect and process the optical signal, eliminating the need for any off-chip optical filters. The on-chip signal processing circuitry improves the desired signal extraction from the optical background noise. Since the IC is manufactured using standard commercial fabrication processes with no post-processing necessary, the system can ultimately be low cost to fabricate. Additionally, because of the CMOS integration, it will consume little power when operating, and even less during stand-by.

Geriatric nutritional risk index predicts all-cause mortality in the oldest-old patients with acute coronary syndrome: A 10-year cohort study.

Background and objective: Nutritional status assessment in acute coronary syndrome (ACS) patients has been neglected for a long time. The geriatric nutritional risk index (GNRI) is a sensitive indicator for assessing the nutritional status of the elderly. This study aims to explore the association between GNRI and all-cause mortality in the oldest-old patients with ACS. Methods: The patients who met the inclusion criteria were consecutively enrolled from January 2006 to December 2012. Clinical data were collected on admission, and all subjects were followed after being discharged. The nutritional status was evaluated using GNRI. The relationship between GNRI and all-cause mortality was assessed by using different analyses. Results: A total of 662 patients with a mean age of 81.87 ± 2.14 years old were included in our study, and followed (median: 63 months, IQR 51-71). Patients whose GNRI ≤ 98 were reported as at risk of malnutrition (31.11%, n = 206). In multivariable analysis, we found that for each SD increase in GNRI, the risk of all-cause mortality lowered by 23%, and the HR for GNRI ≤ 98 was 1.39 (95% CI 1.04-1.86). After stratifying patients into three groups by tertiles of GNRI, we found that the HRs for tertile 2 and tertile 3 were 1.49 (95% CI 1.02-2.19) and 1.74 (95% CI 1.22-2.50), respectively. The trend test revealed a dose-response relationship between GNRI and all-cause mortality in the oldest-old with ACS. Lastly, in subgroup analyses, we found a reliable association between GNRI and all-cause mortality. Conclusion: Malnutrition is common in the oldest-old patients with ACS, and GNRI could predict their long-term all-cause mortality in a dose-dependent manner. GNRI may be a prospective index for risk-stratification and secondary-prevention in the oldest-old patients with ACS.

Wnt 3a Protects Myocardial Injury in Elderly Acute Myocardial Infarction by Inhibiting Serum Cystatin C/ROS-Induced Mitochondrial Damage.

Aging represents an independent risk factor affecting the poor prognosis of patients with acute myocardial infarction (AMI). This present research aimed to explore the molecular mechanism of myocardial injury in elderly AMI by animals and cells experiment. Our previous clinical study found the serum Cystatin C (Cys-C) increased in the elderly AMI population, while the mechanism underlying high Cys-C induced myocardial injury of AMI remains unclear. In the in-vitro study, we confirmed that Wnt/ß-catenin could significantly reduce the expression of cytoplasmic Cys-C through transnuclear action, and highly attenuate the occurrence of mitochondrial oxidative stress injury induced via Cys-C/reactive oxygen species (ROS). Furthermore, the addition of exogenous Wnt3a and inhibition of Cys-C expression could effectively inhibit mitochondrial oxidative stress injury and relieve the acute myocardial hypoxia injury. These results indicate that Cys-C exerted damaging effects on the hypoxic aging cardiomyocyte through the ROS/mitochondrial signaling pathway. Inhibition of this pathway effectively reduced the apoptosis of aging cardiomyocytes. In the in-vivo study, we also explored the function of the Wnt/Cys-C pathway on the ischemic infarction heart. We confirmed that Wnt/ß-catenin served as the upstream protective protein of this pathway, and the promotion of this pathway improved the cardiac structure and function of the elderly AMI mice effectively.

Intracoronary artery retrograde thrombolysis for ST-segment elevation myocardial infarction with a tortuous coronary artery: A case report and review of the literature.

Background: How to deal with large thrombus burdens of culprit's blood vessel remains a great challenge in the treatment of acute myocardial infarction. Case presentation: A 32-year-old Chinese man was diagnosed with ST-segment elevation myocardial infarction (STEMI). Coronary angiography revealed that the distal end of a tortuous left circumflex was completely occluded by a large amount of thrombus. Cutted balloon-directed intracoronary artery retrograde thrombolysis (ICART) with urokinase led to the restoration of coronary blood flow. Because there was no obvious plaque rupture or artery stenosis in the coronary artery, it was only dilated, and no stent was implanted. Conclusion: Cutted balloon-directed ICART can be performed effectively and safely in some STEMI patients with tortuous coronary vessels and large thrombus. (REST or named ICART ClinicalTrials.gov number, ChiCTR1900023849).

Intracoronary artery retrograde thrombolysis combined with percutaneous coronary interventions for ST-segment elevation myocardial infarction complicated with diabetes mellitus: A case report and literature review.

Background: The management of a large thrombus burden in patients with acute myocardial infarction and diabetes is still a worldwide problem. Case presentation: A 74-year-old Chinese woman presented with ST-segment elevation myocardial infarction (STEMI) complicated with diabetes mellitus and hypertension. Angiography revealed massive thrombus formation in the mid-segment of the right coronary artery leading to vascular occlusion. The sheared balloon was placed far from the occlusion segment and urokinase (100,000 u) was administered for intracoronary artery retrograde thrombolysis, and thrombolysis in myocardial infarction (TIMI) grade 3 blood flow was restored within 7 min. At last, one stent was accurately implanted into the culprit's vessel. No-reflow, coronary slow flow, and reperfusion arrhythmia were not observed during this process. Conclusion: Intracoronary artery retrograde thrombolysis (ICART) can be effectively and safely used in patients with STEMI along with diabetes mellitus and hypertension, even if the myocardial infarction exceeds 12 h (REST or named ICART ClinicalTrials.gov number, ChiCTR1900023849).

Single-cell transcriptomic analysis of the tumor ecosystem of adenoid cystic carcinoma.

Adenoid cystic carcinoma (ACC) is a malignant tumor that originates from exocrine gland epithelial cells. We profiled the transcriptomes of 49,948 cells from paracarcinoma and carcinoma tissues of three patients using single-cell RNA sequencing. Three main types of the epithelial cells were identified into myoepithelial-like cells, intercalated duct-like cells, and duct-like cells by marker genes. And part of intercalated duct-like cells with special copy number variations which altered with MYB family gene and EN1 transcriptomes were identified as premalignant cells. Developmental pseudo-time analysis showed that the premalignant cells eventually transformed into malignant cells. Furthermore, MYB and MYBL1 were found to belong to two different gene modules and were expressed in a mutually exclusive manner. The two gene modules drove ACC progression into different directions. Our findings provide novel evidence to explain the high recurrence rate of ACC and its characteristic biological behavior.

MKP-1 Overexpression Reduces Postischemic Myocardial Damage through Attenuation of ER Stress and Mitochondrial Damage.

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress contribute to postischemic myocardial damage, but the upstream regulatory mechanisms have not been identified. In this study, we analyzed the role of mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) in the regulation of mitochondrial function and ER stress in hypoxic cardiomyocytes. Our results show that MKP-1 overexpression sustains viability and reduces hypoxia-induced apoptosis among H9C2 cardiomyocytes. MKP-1 overexpression attenuates ER stress and expression of ER stress genes and improves mitochondrial function in hypoxia-treated H9C2 cells. MKP-1 overexpression also increases ATP production and mitochondrial respiration and attenuates mitochondrial oxidative damage in hypoxic cardiomyocytes. Moreover, our results demonstrate that ERK and JNK are the downstream signaling targets of MKP-1 and that MKP-1 overexpression activates ERK, while it inhibits JNK. Inhibition of ERK reduces the ability of MKP-1 to preserve mitochondrial function and ER homeostasis in hypoxic cardiomyocytes. These results show that MKP-1 plays an essential role in the regulation of mitochondrial function and ER stress in hypoxic H9C2 cardiomyocytes through normalization of the ERK pathway and suggest that MKP-1 may serve as a novel target for the treatment of postischemic myocardial injury.

Evaluation of the prognostic ability of serum uric acid for elderly acute coronary syndrome patients with diabetes mellitus: a prospective cohort study.

OBJECTIVES: This study evaluated the prognostic power of serum uric acid (UA) in predicting adverse events in elderly acute coronary syndrome (ACS) patients with diabetes mellitus (DM). METHODS: The analysis involved 718 ACS patients |>80 years old whose general clinical data and baseline blood biochemical indicators were collected prospectively from January 2006 to December 2012. These patients were classified into two groups based on DM status, and then followed up after discharge. The Kaplan-Meier method was used for major adverse cardiac event (MACE) rates and all-cause mortality. Multivariate Cox regression was performed to analyze the relationship between UA level and long-term clinical prognosis. Receiver operating characteristic (ROC) curves were analyzed to predict the cutoff value of UA in elderly ACS patients with DM. There were 242 and 476 patients in the DM and non-DM (NDM) groups, respectively, and the follow-up time after discharge was 40‒120 months (median, 63 months; interquartile range, 51‒74 months). RESULTS: The all-cause mortality, cardiac mortality, and MACE rates in both DM and NDM patients were higher than those in the control group (P=0.001). All-cause mortalities, cardiac mortalities, and MACE rates in DM patients with moderate and high UA levels were significantly higher than those in the NDM group (P=0.001). Long-term survival rates decreased significantly with increased UA levels in the ACS groups (P=0.001). UA (odds ratio (OR)=2.106, 95% confidence interval (CI)=1.244‒3.568, P=0.006) was found to be an independent risk factor for all-cause mortality and MACE in elderly ACS patients with DM. The cutoff value of UA was 353.6 µmol/L (sensitivity, 67.4%; specificity, 65.7%). CONCLUSIONS: Serum UA level is a strong independent predictor of long-term all-cause death and MACE in elderly ACS patients with DM.

Exenatide inhibits NF-κB and attenuates ER stress in diabetic cardiomyocyte models.

Exenatide is used to treat patients with type-2 diabetes and it also exerts cardioprotective effects. Here, we tested whether Exenatide attenuates hyperglycemia-related cardiomyocyte damage by inhibiting endoplasmic reticulum (ER) stress and the NF-κB signaling pathway. Our results demonstrated that hyperglycemia activates the NF-κB signaling pathway, eliciting ER stress. We also observed cardiomyocyte contractile dysfunction, inflammation, and cell apoptosis induced by hyperglycemia. Exenatide treatment inhibited inflammation, improved cardiomyocyte contractile function, and rescued cardiomyocyte viability. Notably, re-activation of the NF-κB signaling pathway abolished Exenatide's protective effects on hyperglycemic cardiomyocytes. Taken together, our results demonstrate that Exenatide directly reduces hyperglycemia-induced cardiomyocyte damage by inhibiting ER stress and inactivating the NF-κB signaling pathway.

Cardioprotective Role of Melatonin in Acute Myocardial Infarction.

Melatonin is a pleiotropic, indole secreted, and synthesized by the human pineal gland. Melatonin has biological effects including anti-apoptosis, protecting mitochondria, anti-oxidation, anti-inflammation, and stimulating target cells to secrete cytokines. Its protective effect on cardiomyocytes in acute myocardial infarction (AMI) has caused widespread interest in the actions of this molecule. The effects of melatonin against oxidative stress, promoting autophagic repair of cells, regulating immune and inflammatory responses, enhancing mitochondrial function, and relieving endoplasmic reticulum stress, play crucial roles in protecting cardiomyocytes from infarction. Mitochondrial apoptosis and dysfunction are common occurrence in cardiomyocyte injury after myocardial infarction. This review focuses on the targets of melatonin in protecting cardiomyocytes in AMI, the main molecular signaling pathways that melatonin influences in its endogenous protective role in myocardial infarction, and the developmental prospect of melatonin in myocardial infarction treatment.

Effects of carbon nanotube-mediated Caspase3 gene silencing on cardiomyocyte apoptosis and cardiac function during early acute myocardial infarction.

RNA interference (RNAi) technology can achieve efficient and specific silencing of Caspase3 gene expression, thus providing new options for anti-apoptosis treatment. However, delivering siRNA to specific cells and tissues in the body is a significant challenge. Therefore, we aim to construct a functionalized single-walled carbon nanotube (F-CNT) bound to siRNA from Caspase3. The obtained gene transfer carrier F-CNT-siCas3 not only demonstrated a good water solubility and biocompatibility, but also had a high transfection efficiency of up to 82%, which significantly downregulated the expression level of the Caspase3 gene miRNA and protein in primary cardiomyocytes. Furthermore, it was verified by in vivo experiments that Caspase3 gene silencing had obvious protective effects on myocardial cell apoptosis, ventricular remodeling, and cardiac function in Sprague-Dawley (SD) rats after coronary artery ligation. This study may provide an important theoretical basis for the application of F-CNT in vivo siRNA gene therapy to treat cardiovascular diseases.