Creatine Kinase MB Isoform Research Articles

Clinical significance of R-wave amplitude in lead V1 and inferobasal myocardial infarction in patients with inferior wall myocardial infarction.

To assess electrocardiogram (ECG) for risk stratification in inferior ST-elevation myocardial infarction (STEMI) patients within 24 h. Three hundred thirty-four patients were divided into four ECG-based groups: Group A: R V1 <0.3 mV with ST-segment elevation (ST↑) V7-V9, Group B: R V1 <0.3 mV without ST↑ V7-V9, Group C: R V1 ≥0.3 mV with ST↑ V7-V9, and Group D: R V1 ≥0.3 mV without ST↑ V7-V9. Group A demonstrated the longest QRS duration, followed by Groups B, C, and D. ECG signs for right ventricle (RV) infarction were more common in Groups A and B (p < .01). ST elevation in V6, indicative of left ventricle (LV) lateral injury, was more higher in Group C than in Group A, while the ∑ST↑ V3R + V4R + V5R, representing RV infarction, showed the opposite trend (p < .05). The estimated LV infarct size from ECG was similar between Groups A and C, yet Group A had higher creatine kinase MB isoform (CK-MB; p < .05). Cardiac troponin I (cTNI) was higher in Groups A and C than in B and D (p < .05 and p = .16, respectively). NT-proBNP decreased across groups (p = .20), with the highest left ventricular ejection fraction (LVEF) observed in Group D (p < .05). Group A notably demonstrated more cardiac dysfunction within 4 h post-onset. For inferior STEMI patients, concurrent R V1 <0.3 mV with ST↑ V7-V9 suggests prolonged ventricular activation and notable myocardial damage. RV infarction's dominance over LV lateral injury might explain these observations.

CRIF1 attenuates doxorubicin-mediated mitochondrial dysfunction and myocardial senescence via regulating PXDN.

CR6-interacting factor 1 (CRIF1), a multifunctional protein that affects mitochondrial function and cell senescence, plays a regulatory role in heart-related diseases. However, whether CRIF1 participates in myocardial senescence by regulating mitochondrial function remains unclear. Doxorubicin (DOX)-induced C57BL/6 mice to construct mouse myocardial senescence model, and the myocardial function indicators including lactate dehydrogenase (LDH) and Creatine kinase isoform MB (CK-MB) were assessed. The expression of CRIF1 was detected by western blot. Myocardial pathological changes were examined by transthoracic echocardiography and haematoxylin and eosin (H&E) staining. Cell senescence was detected by SA-β-gal staining. JC-1 staining was used to detect mitochondrial membrane potential. Biochemical kits were used to examine oxidative stress-related factors. Additionally, AC16 cardiomyocytes were treated with DOX to mimic the cellular senescence model in vitro. Cell activity was detected by cell counting kit-8 (CCK-8) assay. Co-immunoprecipitation (CO-IP) was used to verify the relationship between CRIF1 and peroxidasin (PXDN). The CRIF1 expression was significantly decreased in DOX-induced senescent mice and AC16 cells. Overexpression of CRIF1 significantly ameliorated DOX-induced myocardial dysfunction and myocardial senescence. Additionally, CRIF1 overexpression attenuated DOX-induced oxidative stress and myocardial mitochondrial dysfunction. Consistently, CRIF1 overexpression also inhibited DOX-induced oxidative stress and senescence in AC16 cells. Moreover, CRIF1 was verified to bind to PXDN and inhibited PXDN expression. The inhibitory effects of CRIF1 overexpression on DOX-induced oxidative stress and senescence in AC16 cells were partly abolished by PXDN expression. CRIF1 plays a protective role against DOX-caused mitochondrial dysfunction and myocardial senescence partly through downregulating PXDN.

Myocardial injury and inflammation following pulsed-field ablation and very high-power short-duration ablation for atrial fibrillation.

Pulmonary vein isolation (PVI) using radiofrequency ablation (RFA) is an established treatment strategy for atrial fibrillation (AF). To improve PVI efficacy and safety, high-power short-duration (HPSD) ablation and pulsed-field ablation (PFA) were recently introduced into clinical practice. This study aimed to determine the extent of myocardial injury and systemic inflammation following PFA, HPSD, and standard RFA using established biomarkers. We included 179 patients with paroxysmal AF receiving first-time PVI with different ablation technologies: standard RFA (30-40 W/20-30 s, n = 52), power-controlled HPSD (70 W/5-7 s, n = 60), temperature-controlled HPSD (90 W/4 s, n = 32), and PFA (biphasic, bipolar waveform, n = 35). High-sensitivity cardiac troponin T (hs-cTnT), creatine kinase (CK),CK MB isoform(CK-MB), and white blood cell (WBC) count were determined before and after ablation. Baseline characteristics were well-balanced between groups (age 63.1 ± 10.3 years, 61.5% male). Postablation hs-cTnT release was significantly higher with PFA (1469.3 ± 495.0 ng/L), HPSD-70W (1322.3 ± 510.6 ng/L), and HPSD-90W (1441.2 ± 409.9 ng/L) than with standard RFA (1045.9 ± 369.7 ng/L; p < .001). CK and CK-MB release was increased with PFA by 3.4-fold and 5.8-fold, respectively, as compared to standard RFA (p < .001). PFA was associated with the lowest elevation in WBC (Δ1.5 ± 1.5 × 109 /L), as compared to standard RFA (Δ3.8 ± 2.5 × 109 /L, p < .001), HPSD-70W (Δ2.7 ± 1.7 × 109 /L, p = .037), and HPSD-90W (Δ3.6 ± 2.5 × 109 /L, p < .001). Among the four investigated ablation technologies, PFA was associated with the highest myocardial injury and the lowest inflammatory reaction.

Screening for Antibody Specificity and Sensitivity with ELISA.

Monoclonal antibodies (MAbs) can be used to detect and quantify protein biomarker antigens (Ag). Systematic screening with an enzyme-linked immunosorbent assay (Butler, J Immunoass, 21(2-3):165-209, 2000) [1] can be used to identify matched Ab-Ag pairs. A method is described for identifying MAbs that recognize cardiac biomarker creatine kinase isoform MB. Cross-reactivity with skeletal muscle biomarker creatine kinase isoform MM and brain biomarker creatine kinase isoform BB is also examined.

Caffeic acid and ferulic acid can improve toxicological damage caused by iron overload mediated by carbonic anhydrase inhibition

The iron ion is an essential element for most forms of life, however, it can damage biological systems when found in free form. Chelation therapy is very important, but it is precarious. Caffeic and ferulic acid are antioxidant compounds with many properties described in research such as anti-inflammatory, antiobesogenic, antithrombotic, vasodilator, and anti-tumor. The aim of the study was to evaluate presenting an in silico approach on the toxicity and bioavailability of caffeic and ferulic acid, subsequently, evaluating them in an iron overload model in vivo and providing a pharmacophoric model through molecular docking. The predictive in silico test did not show relevant toxicity of the compounds, therefore, the in vivo test was performed. The rats received dextran iron and the test groups received caffeic and ferulic acid orally for six weeks. Biochemical, hematological parameters, and tissue oxidative stress marker were analyzed. The experimental model showed increased serum iron levels and changes in several serum parameters such as glucose (215.8 ± 20.3 mg/dL), ALT (512.2 ± 128.7 U/L), creatine kinase (186.8 ± 30.1 U/L), and creatine kinase isoform MB (373.3 ± 69.7 U/L). Caffeic acid and, to a lessed degree, ferullic acid, attenuated the effects of iron overload on the rat serum biochemical parameters. Docking showed a pharmacophoric model where carbonic anhydrase interacted with the test molecules and caffeic acid showed less energy expenditure in this interaction. The results illustrate a new therapeutic action of phenolic compounds on iron overload. The possible interference of carbonic anhydrase in iron metabolism needs to be elucidated.

The latest cutoff value of high-sensitivity cardiac troponin I (access hs-TnI) for major adverse cardiac events during the perioperative period of coronary artery bypass grafting: a retrospective study from a single heart center

Abstract Objectives To investigate the latest cutoff value of high-sensitivity cardiac troponin I for major adverse cardiac events (MACEs) during the perioperative period of coronary artery bypass grafting (CABG). Methods A total of 200 patients, into MACEs and non-MACEs groups according to the occurrence of MACEs over a 12 day postoperative period underwent a complete baseline history survey, physical examination, 12-lead electrocardiogram (ECG), and laboratory examination during a preoperative cardiology consultation. Serum levels of hs-TnI, myohemoglobin, creatine kinase MB isoform (CK-MB), and B-type natriuretic peptide were assessed using a Beckman DXI800 automatic chemiluminescence immune analyzer. Results The 200 patients were classified into the MACEs (n=10) and non-MACEs (n=190) groups. Based on a receiver-operating characteristic analysis, the optimal 4–6 h postoperative hs-TnI, CK-MB, and MYO joint cut-off levels for predicting perioperative MACEs were 2,622.3 pg/mL, 17.9 ng/mL, and 190.2 ng/mL, respectively. The AUC was 0.779 (95% confidence interval: 0.622–0.937; p&lt;0.05) with a sensitivity of 80.0% and a specificity of 74.0%. When the hs-TnI, CK-MB, and MYO levels exceeded the joint cut-off levels, the incidence of MACEs was significantly increased during the perioperative period (Log rank p&lt;0.05). Cox regression analysis showed that dyslipidemia, left ventricular ejection fraction &lt;50%, hs-TnI level, and myohemoglobin level were the main risk factors for MACEs after CABG (p&lt;0.05). Conclusion An hs-TnI level of 2,622.3 pg/mL, CK-MB level of 17.9 ng/mL, and MYO level of 190.2 ng/mL were the cutoff values for predicting MACEs. Dyslipidemia, left ventricular ejection fraction &lt;50%, hs-TnI level, and myohemoglobin level were the main risk factors for MACEs after CABG.

Predictive value and regulatory mechanism of serum miR-499a-5p on myocardial dysfunction in sepsis

BackgroundThis study sought to investigate the predictive value and regulatory mechanism of serum miR-499a-5p in sepsis-induced myocardial dysfunction (SIMD).MethodsA total of 60 patients with sepsis and 60 healthy volunteers were enrolled in this study. The serum levels of miRNAs (miR-451, miR-378 and miR-499a-5p) were detected. Receiver operating characteristic curve and logistic regression analysis were used to evaluate the diagnostic and prognostic value of miR-499a-5p in SIMD patients. AC16 cells were used to establish SIMD model in vitro using lipopolysaccharide (LPS). An analysis was conducted for miR-499a-5p expression, cell viability, and the concentration of creatine kinase-MB isoform (CK-MB), brain natriuretic peptide (BNP), superoxide dismutase (SOD) and cytochrome C oxidase IV (COX IV). The downstream target of miR-499a-5p was verified.ResultsOur results revealed a poor expression of miR-499a-5p in the serum of SIMD patients, while no significant difference was evident for miR-451 and miR-378. The level of miR-499a-5p in the survival group was higher than the non-survival group. miR-499a-5p elicited good diagnostic and prognostic value for SIMD. Our findings revealed that miR-499a-5p was decreased significantly in LPS-treated cardiomyocytes. After overexpression of miR-499a-5p, the cell viability increased, and the concentrations of CK-MB and BNP were decreased, while the concentrations of SOD and COX IV were increased. EIF4E was validated as the target of miR-499a-5p. After overexpression of EIF4E, the cell viability was decreased and the concentrations of CK-MB and BNP were increased while the concentrations of SOD and COX IV were decreased.ConclusionThe level of miR-499a-5p is weak in SIMD patients. miR-499a-5p has a good diagnostic and prognostic value for SIMD by inhibiting EIF4E transcription.

The relationship between non-alcoholic fatty liver disease and acute coronary syndrome severity: is non-alcoholic fatty liver disease a risk marker of coronary atherosclerotic disease?

Abstract Background/Introduction Non-alcoholic fatty liver disease (NAFLD) has been significantly associated with atherosclerotic disease independent of classical risk factors. However, the role of NAFLD in this context remains unclear. The systemic inflammation described in NAFLD related to liver disease progression may be one factor that can influence the progression and instability of atherosclerotic disease and, consequently, in the clinical characteristics of acute coronary syndrome (ACS). Purpose To assess the potential relationship between NAFLD and ACS severity. Methods We performed a retrospective study in adult patients with ACS who presented to the emergency room of a quaternary care medical centre between March 2015 and March 2016 and selected 99 patients without previously known coronary artery disease or liver disease, without a history of significant alcohol consumption, terminal disease, other acute illness, use of statins, amiodarone, or other steatogenic drugs. The diagnostic criteria for acute myocardial infarction (AMI) with ST-segment elevation (STEMI) were ST elevation ≥1mm in ≥2 contiguous leads (2mm for leads V1 to V3). The acute myocardial infarction without ST-segment elevation (NSTEMI) diagnostic was established in patients who did not meet the criteria for STEMI and who had elevated necrosis markers (creatine kinase-MB isoform and troponin I). Unstable angina (UA) diagnostic was established in patients who did not meet the criteria for STEMI and NSTEMI but had more than three cardiovascular risk factors and typical thoracic pain. The presence of steatosis and its degrees was assessed using ultrasound, and the diagnosis of NAFLD was based on the presence of steatosis and clinical history. Results The diagnosis of UA, NSTEMI and STEMI was established in 40, 33 and 26 patients, respectively, and NAFLD was observed in 30%, 66.6% and 76.9% of these patients. NAFLD patients were 5.8 times more likely to have a diagnosis of AMI than UA (p&amp;lt;0.001), were 7.88 times more likely to have a diagnosis of STEMI than UA (p&amp;lt;0.001) and were 4.7 times more likely to have a diagnosis of NSTEMI than UA (p&amp;lt;0.01). Patients with grades 2 and 3 liver steatosis were 4.2 times more likely to have a diagnosis of AMI than UA (p&amp;lt;0.01) and were 8.2 times more likely to have a diagnosis of STEMI than UA (p&amp;lt;0.01). There was no significant relationship between other variables evaluated and the clinical presentation of ACS. Conclusion(s) In this study, the frequency of AMI presentation in NAFLD patients with ACS was significantly higher than the frequency of UA, suggesting a significant relationship between NAFLD and the severity of ACS, independent of the classic risk factors assessed. The results also suggest that the steatosis degree can proportionally influence this context. Therefore, NAFLD could be considered a potential risk marker for coronary atherosclerotic disease progression and instability. Funding Acknowledgement Type of funding sources: None.

Test Volume Ratio Benchmarking to Identify and Reduce Low-Value Laboratory Utilization.

We analyzed test volume data to identify low-value test utilization. We subsequently tracked the efficacy of interventions to improve test utilization by decreasing low-value testing. Test volume data for analytes included in the Choosing Wisely guidelines were analyzed to identify population outliers. Outliers were defined by test volume ratios of either analyte to sodium or paired analytes to correct for variation in patient volumes at each site. Interventions to improve test utilization were targeted to outlier sites. Relative efficacy in reducing low-value testing was tracked at those sites. After appropriate data cleaning, test volume ratios for 17 analytes paired with sodium and 8 pairs of analytes were acquired from 108 national sites. A site with abnormally high Clostridium difficile/sodium ratio was selected for intervention, leading to a 71% decrease in C difficile tests. Two different interventions to decrease creatine kinase MB isoform (CKMB) testing were performed at two unique sites with abnormally high CKMB/troponin ratios. These interventions decreased CKMB by 11% and 98% at the different sites, showing the efficacy of the different kinds of interventions. Test volume ratio analysis and benchmarking enable identification of low-value test utilization.

Myocardial Injury After Temporary Transvenous Cardiac Pacing.

IntroductionTemporary transvenous cardiac pacing (TTCP) can lead to potential penetration and occasional perforation of the right ventricular wall. No study to date has analyzed the effect of TTCP on myocardial injury by cardiac troponin (cTn) measurement. The present study was designed to investigate perioperative myocardial injury in elective TTCP in noncardiac surgical settings.Patients and MethodsThis retrospective study investigated the data collected from August 2018 through March 2020 from 22 eligible patients who underwent elective TTCP for noncardiac procedures. The patients had a median age of 66 (50–83) years; six (27.3%) of them were women, and all of them had a baseline cTn <1 upper reference limit (URL). Cardiac biomarker assays were performed before and after TTCP, and their results were compared.ResultsAfter TTCP, cTn > 1 URL was detected in 20 (91%, N=22) patients. Among these 22 patients, paired t-test comparing assay results before and after TTCP lead insertion showed a mean cTn elevation of 3.599 URL (95% CI: 1.566 to 5.632, P<0.01), and a mean creatine kinase-MB isoform elevation of 0.1550 URL (95% CI: −0.01239 to 0.3224, P>0.05).ConclusionThe study demonstrates a high incidence of myocardial injury associated with TTCP, which should be a matter of concern for the involved physicians.

Biomarkers assessment in patients with Chagas disease and systemic arterial hypertension.

Chagas disease (ChD) and systemic arterial hypertension (SAH) are two severe comorbidities that lead to mortality and a reduction in people's quality of life, with an impact on public health. The aim of this study was to quantify the biomarkers of cardiac injury in patients with ChD and SAH. Eighty patients were divided into four groups: 20 hypertensive patients, 20 ChD-hypertensive patients, 20 ChD patients, and 20 normotensive volunteers; all of them came from outpatient's public health services. Among the evaluated markers for cardiac lesions (creatine kinase, creatine kinase-MB isoform, myoglobin, high-sensitive cardiac troponin T[hs-cTnT], B-type natriuretic peptide [BNP], and C-reactive protein), hs-cTnT and BNP were the most appropriate. Importantly, our results showed that the cutoff point for hs-cTnT could be < 0.007ng/mL, which could lead to the early detection of myocardial lesions. The BNP and hs-cTnT levels were high only in the ChD and ChD-hypertensive patient groups, suggesting that Chagas' disease may play an important role in the increase of these biomarkers. ChD patients, hypertensive or not, with cardiac or cardiodigestive involvement presented significantly higher values of hs-cTnT (p < 0.001) and BNP (p = 0.001) than ChD patients with indeterminate and digestive forms, which strengthens the validation of these markers for the follow-up of clinical cardiac form of ChD. This study suggests that the BNP and hs-cTnT can be used as possible indirect biomarkers of cardiac damage. In addition, the reference values of these biomarkers in Chagas and hypertensive cardiomyopathies should be better understood with further studies.

Correlation of plasma N-acetyl-neuraminic acid level with TIMI risk stratification and clinical outcomes in patients with acute coronary syndrome

To explore the correlation of plasma N-acetyl-neuraminic acid level with Thrombolysis In Myocardial Infarction (TIMI) risk score and clinical outcomes of patients with acute coronary syndrome (ACS). We consecutively enrolled 708 consecutive patients (401 male and 307 female, mean age 63.6±10.6 years) undergoing coronary angiography in our hospital between October, 2018 and July, 2019, including 597 patients with ACS and 111 without ACS (control group). The patients with ACS group were divided into high (n=104), moderate (n=425) and low (n=68) risk groups according to their TIMI risk scores. All the participants were examined for plasma Neu5Ac level using liquid chromatography-tandem mass spectrometry and underwent coronary angiography with their Gensini scores calculated. The patients with ACS were followed up after discharge for a mean of 15 months for the occurrence of major adverse cardiac events (Mace). Binary logistic regression analysis was performed to identify the risk factors of Mace in these patients. Plasma Neu5Ac levels were significantly higher in ACS group than in the control group (P < 0.05). ROC curve analysis showed that plasma Neu5Ac level could assist in the diagnosis of ACS (0.648 [0.597-0.699]) with a sensitivity of 39.2% and a specificity of 86.5% at the cutoff value of 288.50 ng/mL. In the ACS patients, plasma Neu5Ac level was significantly higher in the high-risk group than in the moderate-risk and low-risk groups (P < 0.05) and could assist in the diagnosis of a high risk (0.645 [0.588-0.703]) with a sensitivity of 42.3% and a specificity of 80.1% at the cutoff value of 327.50 ng/ mL. Plasma Neu5Ac was positively correlated with age, serum uric acid, creatinine, lipoprotein a, Ddimer, C-reactive protein, MB isoform of creatine kinase and Gensini score and negatively correlated with high-density lipoprotein level. During the followup, 80 ACS patients experienced Mace, who had significantly higher plasma Neu5Ac level than those without Mace (n=517). Logistic regression analysis showed that plasma Neu5Ac level and a history of previous stroke were independent risk factors for the occurrence of Mace. Plasma Neu5Ac level can provide assistance in the diagnosis and risk stratification of ACS and is an independent risk factor for prognosis of ACS patients.

Correlation of serum N-Acetylneuraminic acid with the risk and prognosis of acute coronary syndrome: a prospective cohort study

BackgroundN-acetylneuraminic acid (Neu5Ac) is a functional metabolite involved in coronary artery disease (CAD). We aimed to evaluate the relationship between serum Neu5Ac and the risk and prognosis of acute coronary syndrome (ACS) in a real-world prospective study.MethodsPatients with suspected ACS who underwent coronary angiography were included. Serum Neu5Ac was measured at admission. Coronary lesion severity was evaluated by Gensini Score. GRACE risk stratification was performed at admission. Major adverse cardiac events (MACEs) were recorded during follow-up.ResultsA total of 766 patients, including 537 with unstable angina (UAP), 100 with myocardial infarction (MI), and 129 without CAD were included. The circulating Neu5Ac level was significantly higher in patients with MI (median [1QR]: 297[220, 374] ng/ml) than in those with UAP (227 [114, 312] ng/ml) or without CAD (207 [114, 276] ng/ml; both p < 0.001). Serum level of Neu5Ac was positively correlated with age, hypertension, serum uric acid, creatinine, MB isoform of creatine kinase (CK-MB), and Gensini score (all p < 0.05). Receiver operating characteristic curve analysis showed that a higher serum Neu5Ac was potentially associated with MI and high-risk GRACE stratification in ACS patients. Logistic analysis identified only elevated serum Neu5Ac as an independent predictor of MACEs in these patients (odds ratio [OR]: 1.003, 95% confidence interval [CI]: 1.002–1.005, p < 0.001).ConclusionsSerum Neu5Ac is associated with myocardial injury, GRACE risk category, and prognosis in ACS patients.

The impact of an ultra-trail on the dynamic of cardiac, inflammatory, renal and oxidative stress biological markers correlated with electrocardiogram and echocardiogram

The aim of this study was to describe the effects of a 64.2 km ultra-trail on the biomarkers of muscle damage, inflammation and oxidative stress, and compare the results observed with an ECG and an echocardiogram, both performed before and after the race. Thirty-three ultra-trail volunteers (45.8 ± 8.7 years old) were enrolled in our study. Three blood tests were drawn from each runner, one just before (TPRE), one just after (TPOST) and the last 3 h after the end of the race (TPOST3h). All the markers increased. The maximum concentrations observed were at TPOST3h and were significant (p < 0.001) for creatine kinase, creatine kinase isoform MB, high-sensitivity C-reactive protein, uric acid and for the ratio of reduced glutathione to oxidised glutathione. However, in the case of myoglobin, high-sensitive troponin T, N-terminal pro-brain natriuretic peptide, oxidised glutathione, myeloperoxidase, cystatin C and creatinine, the most significant increases were at TPOST (p < 0.001). Modifications were observed in the medical imaging using echocardiography such as reduction of left ventricule end-sytolic and diastolic volumes and left ventricular global longitudinal strain. ECG showed electrical criteria for left ventricular hypertrophy and incomplete right bundle branch block after the race. Endurance races cause significant physiological stress to the body that can be measured by the increase of different biomarkers. From a laboratory perspective, it is important to take into account the possible exercise performed previous to the testing to avoid a misinterpretation of the results. From a training perspective, due to these increases in biomarkers, it is recommended that runners wait at least 72 h after an ultra-trail before subsequent training. In addition a transient impairment of ventricular function due to dehydration were observed.

RETRACTED ARTICLE: Downregulation of miR-483-5p decreases hypoxia-induced injury in human cardiomyocytes by targeting MAPK3

BackgroundMiR-483-5p was recently identified as a risk factor in the early stages of acute myocardial infarction (AMI) patients. Here, we further investigated how miR-483-5p affects cardiomyocyte apoptosis and oxidative stress under hypoxic conditions.MethodsPlasma samples were collected from AMI patients and healthy volunteers. The expression of miR-483-5p was determined using quantitative real-time PCR. An in vitro hypoxic model was constructed to mimic AMI in AC16 cells. Cell viability, apoptosis and oxidative stress biomarker levels (MDA, SOD and CAT) were respectively determined using CCK-8, flow cytometry and commercial assay kits.ResultsThe expression levels of miR-483-5p were significantly higher in AMI patients than in control subjects. Circulating levels of miR-483-5p positively correlated with creatine kinase MB isoform (CK-MB) and cardiac troponin I (cTnI) levels. The in vitro experiments showed that the expression levels of miR-483-5p were also upregulated in hypoxia-induced AC16 cell injury. MiR-483-5p overexpression significantly increased hypoxia-induced cardiomyocyte apoptosis and oxidative stress, while knockdown attenuated these effects. Mechanistically, miR-483-5p directly targets MAPK3 in AC16 cells. Furthermore, the protective effects of miR-483-5p knockdown against hypoxia-induced cardiomyocyte injury are partially dependent on MAPK3.ConclusionsMiR-483-5p, which targets MAPK3, might be a potential therapeutic target for the diagnosis and prevention of hypoxia-induced myocardial injury.

Fast skeletal troponin I, but not the slow isoform, is increased in patients under statin therapy: a pilot study.

IntroductionStatin therapy is often associated with muscle complaints and increased serum creatine kinase (CK). However, although essential in determining muscle damage, this marker is not specific for skeletal muscle. Recent studies on animal models have shown that slow and fast isoforms of skeletal troponin I (ssTnI and fsTnI, respectively) can be useful markers of skeletal muscle injury. The aim of this study was to evaluate the utility of ssTnI and fsTnI as markers to monitor the statin-induced skeletal muscle damage.Materials and methodsA total of 51 patients (14 using and 37 not using statins) admitted to the intensive care unit of the University of Ferrara Academic Hospital were included in this observational study. Serum activities of CK, aldolase, alanine aminotransferase and myoglobin were determined by spectrophotometric assays or routine laboratory analysis. Isoforms ssTnI and fsTnI were determined by commercially available ELISAs. The creatine kinase MB isoform (CK-MB) and cardiac troponin I (cTnI) were evaluated as biomarkers of cardiac muscle damage by automatic analysers.ResultsAmong the non-specific markers, only CK was significantly higher in statin users (P = 0.027). Isoform fsTnI, but not ssTnI, was specifically increased in those patients using statins (P = 0.009) evidencing the major susceptibility of fast-twitch fibres towards statins. Sub-clinical increase in fsTnI, but not CK, was more frequent in statin users (P = 0.007). Cardiac markers were not significantly altered by statins confirming the selectivity of the effect on skeletal muscle.ConclusionsSerum fsTnI could be a good marker for monitoring statin-associated muscular damage outperforming traditional markers.

Aldehyde dehydrogenase 2 activation ameliorates cyclophosphamide-induced acute cardiotoxicity via detoxification of toxic aldehydes and suppression of cardiac cell death

Cyclophosphamide (CY)-induced acute cardiotoxicity is a common side effect which is dose dependent. It is reported that up to 20% of patients received high dose of CY treatment suffered from acute cardiac dysfunction. However, the effective intervention strategies and related mechanisms are still largely unknown. We aimed to investigate the effects of aldehyde dehydrogenase 2 (ALDH2), an important endogenous cardioprotective enzyme, on CY-induced acute cardiotoxicity and the underlying mechanisms. It was found that ALDH2 knockout (KO) mice were more sensitive to CY-induced acute cardiotoxicity, presenting as higher serum levels of creatine kinase-MB isoform and lactate dehydrogenase, and significantly reduced myocardial contractility compared with C57BL/6 (WT) mice. In addition, cardiac cell death, especially necrosis, was obviously increased in ALDH2 KO mice compared with WT mice after CY treatment. Furthermore, accumulation of toxic aldehydes such as acrolein and 4-HNE and reactive oxygen species (ROS) in the myocardium were significantly elevated after CY in ALDH2 KO mice. Importantly, ALDH2 activation by Alda-1 pretreatment markedly attenuated CY-induced accumulation of toxic aldehydes, cardiac cell death and cardiac dysfunction, without affecting CY's anti-tumor efficacy. In conclusion, the cardioprotective effects of ALDH2 activation against CY-induced acute cardiotoxicity are exerted via reducing toxic aldehydes accumulation and potentially interrupting the acrolein-ROS-aldehydes vicious circles, and thus alleviates myocardial cell death, without antagonizing the anti-tumor efficacy of CY. Therefore, ALDH2 might be a promising prevention and treatment target for CY-induced acute cardiotoxicity.

Complement activation in acute myocardial infarction: An early marker of inflammation and tissue injury?

BackgroundAcute myocardial infarction (AMI) is a potentially fatal condition, being a major cause of death worldwide. Ischemia suffered during AMI causes tissue damage, leading to an inflammatory process. Moreover, myocardial injury can generate damage-associated molecular patterns that activate pattern recognition molecules including some complement proteins. MethodsHere we investigated products of complement activation, C3d and soluble C5b9 (sC5b9), as potential biomarkers for myocardial injury and inflammation, as well as serum cytokines (IL-6 and TNF-alpha), alpha-1-acid glycoprotein (AGP), and classical markers of myocardial necrosis (creatine kinase, creatine kinase-MB isoform, myoglobin and troponin-I) in a longitudinal study of patients with AMI (from admission, 6 h and 12 h post admission, and at discharge from hospital). Individuals undergoing cardiac catheterization (CC) with normal coronary arteries and asymptomatics with no history of cardiovascular disease or invasive procedures were included as controls. ResultsPlasma C3d was higher in AMI at admission, 6 h, 12 h, and discharge vs CC (p < 0.0001; p = 0.0061; p = 0.0081; p = 0.044) and asymptomatic (p = 0.0001 for admission, 6 h and 12 h; p = 0.0002 for discharge). Moreover, sC5b9 was higher only at admission and 6 h vs asymptomatic (p = 0.0031 and p = 0.0019). Additionally, AGP levels were elevated at admission, 6 h, 12 h, and discharge vs asymptomatic (p = 0.0003; p = 0.0289; p = 0.0009, p = 0.0017). IL-6 concentration was low at admission and 6 h and reached a peak at 12 h (p < 0.0001 for all groups). All classical markers of myocardial necrosis presented higher concentration at 6 h. ConclusionsOur results showed that complement activation is an early event in AMI occurring before the elevation of classical markers of myocardial necrosis such as creatine kinase, creatine kinase-MB isoform, myoglobin and troponin-I. These findings indicated C3d and sC5b9 as possible biomarkers for inflammation and tissue damage in AMI.

Salivary biomarkers and cardiovascular disease: a systematic review.

The purpose of this systematic review is to summarize the literature examining associations between salivary biomarkers and cardiovascular disease (CVD) status. An advanced search was conducted using MeSH terms related to salivary biomarkers and CVD, and entered into the PubMed, Web of Science, and Google Scholar search databases. Four hundred and thirty-three records were narrowed to 22 accepted articles. Included titles were assessed for quality using the Newcastle-Ottawa scale, and ranked into categories of low, moderate, or high. A total of 40 salivary biomarkers were analyzed among accepted articles. The most studied markers were salivary creatine kinase isoform MB, C-reactive protein (CRP), matrix metalloproteinase-9, troponin I, myeloperoxidase, myoglobin, and brain natriuretic peptide. Salivary CRP provided the most consistent trends. Statistically significant increases of salivary CRP were present with CVD in every study that analyzed it. The remaining six markers demonstrated varying patterns. Existing studies provide insufficient data to draw definitive conclusions. Current research shows that there is an association between some salivary biomarkers and CVD, but the details of existing studies are conflicting. Despite inconclusive results, the diagnostic potential of saliva shows promise as a non-invasive means of cardiovascular risk assessment.

Prophylactic intra-aortic balloon counterpulsation before surgical myocardial revascularization in patients with acute myocardial infarction.

Prophylactic intra-aortic balloon counterpulsation (pIABC) is recommended for high-risk patients undergoing coronary artery bypass grafting (CABG) surgery. Criteria for high-risk patients benefiting from pIABC are unclear. This study aimed to specifically describe the effect of pIABC on outcomes of patients with acute myocardial infarction (AMI) undergoing CABG. In 178 of 484 AMI patients (non-ST-segment elevation myocardial infarction [NSTEMI] or ST-segment elevation myocardial infarction [STEMI] ≤5 days before surgery) without cardiogenic shock who underwent CABG between 2008 and 2013, pIABC was initiated preoperatively. After propensity score matching, the outcomes of 400 patients were analyzed (pIABC: 150; Control: 250). After propensity score matching, baseline and operative characteristics were balanced between the groups except for a higher rate of patients with a left ventricular ejection fraction (LVEF)≤30% in the pIABC group (26% vs. Control: 13%; p=0.032). Seven point two percent (7.2%) of the control patients received an IABP intraoperatively or postoperatively. Postoperative extracorporeal life support (ECLS) was only needed in the control group (1.2% vs. 0%; p=0.01). Postoperative plasma curves of troponin I, creatine kinase (CK) and creatine kinase isoform MB (CK-MB) levels were reduced in the pIABC group compared with the control group. In-hospital mortality was reduced in the pIABC group (3.3% vs. control: 6.4%; p=0.18). After multivariate adjustment for other preoperative risk factors, pIABC was significantly protective concerning in-hospital mortality (HR 0.56; 95%-CI 0.023-0.74; p=0.021). Mortality (pIABC vs. control) was more affected in patients with preoperative LVEF≤30% (2/36 (5.6%) vs. 6/31 (19%); heart rate (HR) 0.25; 95%-CI 0.046-1.3; p=0.13) compared with LVEF>30% (3/114 (2.6%) vs. 10/219 (4.6%); HR 0.56; 95%-CI 0.15-2.1; p=0.55). Long-term survival did not differ between the groups. pIABC in CABG for AMI is associated with reduced perioperative cardiac injury and in-hospital mortality. Long-term survival is not affected.