Manifestations Of Coronary Heart Disease Research Articles

Cardiac Myosin-binding Protein-C as a Biomarker in the Early Diagnosis of Acute Coronary Syndrome and Differentiation of Its Types

Abstract Background: Coronary heart disease (CHD) is primarily caused by atherosclerotic lesions within the intima of coronary arteries and acute coronary syndrome (ACS) is the main acute clinical manifestation of CHD. The ACS is manifested in one of three subtypes and it is the leading cause of mortality worldwide. The three subtypes of ACS include: acute myocardial infarction (MI) with the electrocardiogram (ECG) presenting ST-segment elevation (STEMI), MI with no ST-segment elevation on ECG (NSTEMI), and the third subtype is unstable angina (UA). The early diagnosis of is important in decreasing morbidity and mortality in ACS patients. Objective: To investigate the role of serum level of cardiac myosin-binding protein-C (cMyC), compared with high-sensitivity cardiac troponin-I (hsCTn-I) in the early diagnosis of ACS and differentiation of its subtypes. Materials and Methods: One hundred and twenty patients (72 males and 48 females), aged ≥30 years selected from those who were admitted to emergency department (ED) of Al-Yarmouk teaching hospital and diagnosed with ACS by cardiologists. The duration between the onset of chest pain and admission to ED should not exceed 3 h in any cohort. Apparenty healthy subjects as controls group for the study were recruited from those who had no current illness, particularly CHD, no other systemic disease and each had a normal ECG. For each study subject, cMybp-C and hsCT-I serum levels on admission were measured using the enzyme-linked immunosorbent assay kits. For each ACS patient, serum level of hsCTn-I level was measured 3 h after admission. Results: The comparison of cMybp-C levels among study groups revealed an overall significant difference and on paired comparison of study groups, the cMybp-C mean level was significantly higher in each ACS subgroup than in controls group (P < 0.001), except in UA subgroup versus controls group. The cMybp-C levels showed a significant positive correlation with hsCT-I levels on admission in STEMI and NSTEMI subgroups but not in UA subgroup. The cMybp-C levels also showed a significant positive correlation with hscT-I levels 3 h after admission in STEMI and NSTEMI subgroups but not in UA subgroup. On receiver operating characteristic curve analysis, the cMybp-C level had a better diagnostic accuracy than hscTn-I on admission in differentiation of patients with “STEMI or NSTEMI” from those with UA or from controls. Conclusion: Serum cMybp-C mean level is significantly higher in ACS patients with STEMI and NSTEMI than in controls and the increase was more significant than hsCTn-I mean level on admission, so it could help the early diagnosis of ACS patients. The serum levels of cMybp-C also had a better diagnostic accuracy than hsCTn-I on admission in differentiation of ACS patients with STEMI or NSTEMI from those with UA or from controls.

Regulatory mechanism of DDX5 in ox-LDL-induced endothelial cell injury through the miR-640/SOX6 axis.

Endothelial dysfunction is an early and pre-clinical manifestation of coronary heart disease (CHD). This study investigates the role of DDX5 in oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell injury to confer novel targets for the treatment of CHD. Endothelial cells were induced by ox-LDL. DDX5, pri-miR-640, pre-miR-640, miR-640, and SOX6 expressions were analyzed by RT-qPCR and Western blot. DDX5 expression was intervened by shRNA, followed by CCK-8 analysis of proliferation, flow cytometry detection of apoptosis, and tube formation assay analysis of angiogenic potential of cells. The binding between DDX5 and pri-miR-640 was determined by RIP, and the pri-miR-640 RNA stability was measured after actinomycin D treatment. Dual-luciferase assay verified the targeting relationship between miR-640 and SOX6. DDX5 and miR-640 were highly expressed while SOX6 was poorly expressed in ox-LDL-induced endothelial cells. Silence of DDX5 augmented cell proliferation, abated apoptosis, and facilitated angiogenesis. Mechanistically, RNA binding protein DDX5 elevated miR-640 expression by weakening the degradation of pri-miR-640, thereby reducing SOX6 expression. Combined experimental results indicated that overexpression of miR-640 or low expression of SOX6 offset the protective effect of DDX5 silencing on cell injury. DDX5 elevates miR-640 expression by repressing the degradation of pri-miR-640 and then reduces SOX6 expression, thus exacerbating ox-LDL-induced endothelial cell injury.

The predictive value of serum fibrinogen and platelet distribution width for long-term cardiac death in acute myocardial infarction patients.

Acute myocardial infarction (AMI) is the most severe manifestation of coronary heart disease (CHD), and timely and effective opening of the culprit vessels has been effective in reducing its mortality, but long-term death still threatens the life of patients. Therefore, finding biomarkers to predict death post-myocardial infarction (MI) is crucial. The aim of our study is to find biomarkers that predicted long-term death in Chinese AMI patients. This retrospective analysis included patients with AMI from 1 January 2017 to 30 September 2019. All patients were followed up at least 4 years. Propensity score matching was used to mitigate the influence of nonrandom selection in MI-survival and MI-death groups. Cox analysis was applied for analyzing the risk factors of death post-MI. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of biomarkers. Of the 1,059 AMI patients analyzed, 130 died during follow-up. After propensity matching, there were 116 patients in each of the two groups. In addition to the traditional risk factors for long-term death post-MI, two important risk factors platelet distribution width (PDW) [hazard ratio (HR) =1.210, 95% confidence interval (CI): 1.080-1.356, P=0.001] and fibrinogen (HR =1.218, 95% CI: 1.027-1.444, P=0.02) were found. The area under the curve (AUC) of PDW and fibrinogen was 0.604 (P=0.007) and 0.684 (P<0.001) respectively. The optimal thresholds were 13.05% and 3.562 g/L respectively. PDW and fibrinogen seem to be useful as biomarkers for long-term death prediction post-MI. The current research provides new insight into the prevention and treatment of death in Chinese patients post-MI.

Routine Coronary Angiography and Functional Cardiac Tests before Resection of Abdominal Aortic Aneurysm in Patients without Symptoms of Myocardial Infarction

INTRODUCTION: Cardiac complications are leaders in the structure of mortality of patients after resection of abdominal aortic aneurysms (AAA). In recent years more data have been obtained on the possibility of performing invasive coronary angiography (CAG) as a method of preoperative assessment of the condition of the coronary arteries. AIM: To assess the tactics of routine CAG and preventive revascularization of the myocardium in comparison with non-invasive functional tests in patients without clinical manifestations of coronary heart disease (CHD) from positions of the hospital outcomes of AAA resections. MATERIALS AND METHODS: A retrospective study included 205 patients without clinical and instrumental signs of CHD who underwent AAA resection at National Medical Research Center of Surgery named after A. Vishnevsky in 2001–2021. Patients of the first group (n = 55) underwent CAG before AAA resection and, if significant stenosis of coronary arteries was detected, revascularization of the myocardium was performed. In patients of the second group (n = 71), only functional cardiac tests were conducted before the operation. Patients of the third group were operated on without additional evaluation of cardiac status. RESULTS: In 30.9% of patients of the first group, significant coronary lesions were detected, in 29.5% of them with the involvement of the left main coronary artery. This required 10 percutaneous coronary interventions and 5 coronary artery bypass surgeries, which made 27.0% of patients in this group. No cases of myocardial infarction were recorded in this group. In the second and third groups, one case of myocardial infarction in each group was recorded (p = 0.688). There was no significant difference in the postoperative mortality in all the groups (1.8%; 4.2%; 2.5%, respectively; p = 0.704). To this end, maximally invasive diagnostic tactics increased the average waiting time for AAA resection: 52.2 ± 6.0 days in groups without coronary angiography and myocardial revascularization versus 99.2 ± 13.0 days in the first group. CONCLUSION: In a cohort of patients without anamnestic and clinical manifestations of coronary artery disease, the tactics of routine coronary angiography followed by prophylactic myocardial revascularization did not improve the short-term results of AAA resection, while the waiting period for intervention on the abdominal aorta increased. Preoperative tactics with functional cardiac tests also did not affect the treatment results.

Analysis of immunoinfiltration and EndoMT based on TGF-β signaling pathway-related genes in acute myocardial infarction

Acute myocardial infarction (AMI), a critical manifestation of coronary heart disease, presents a complex and not entirely understood etiology. This study investigates the potential role of immune infiltration and endothelial-mesenchymal transition (EndoMT) in AMI pathogenesis. We conducted an analysis of the GSE24519 and MSigDB datasets to identify differentially expressed genes associated with the TGF-β signaling pathway (DE-TSRGs) and carried out a functional enrichment analysis. Additionally, we evaluated immune infiltration in AMI and its possible link to myocardial fibrosis. Key genes were identified using machine learning and LASSO logistic regression. The expression of MEOX1 in the ventricular muscles and endothelial cells of Sprague–Dawley rats was assessed through RT-qPCR, immunohistochemical and immunofluorescence assays, and the effect of MEOX1 overexpression on EndoMT was investigated. Our study identified five DE-TSRGs, among which MEOX1, SMURF1, and SPTBN1 exhibited the most significant associations with AMI. Notably, we detected substantial immune infiltration in AMI specimens, with a marked increase in neutrophils and macrophages. MEOX1 demonstrated consistent expression patterns in rat ventricular muscle tissue and endothelial cells, and its overexpression induced EndoMT. Our findings suggest that the TGF-β signaling pathway may contribute to AMI progression by activating the immune response. MEOX1, linked to the TGF-β signaling pathway, appears to facilitate myocardial fibrosis via EndoMT following AMI. These novel insights into the mechanisms of AMI pathogenesis could offer promising therapeutic targets for intervention.

Antifibrotic effects of colchicine on 3T3 cell line ischemia to mitigate detrimental remodeling

Context: Acute myocardial infarction (AMI) is one of the clinical manifestations of coronary heart disease caused by the cessation of coronary blood flow. The development of the management of AMI has resulted in a reduction in the mortality rate of AMI patients. Nevertheless, the apparent inflammation triggers detrimental remodeling, so antifibrotic such as colchicine are needed. Aims: To analyze the impact of colchicine administration on the reduction of ventricular remodeling through the NLRP3 inflammasome, TGF-β, and α-SMA in a 3T3 cell line culture under ischemic conditions. Methods: The 3T3 cell line culture underwent ischemia treatment using CoCl2 and subsequent treatment with colchicine. This treatment was conducted for 24 hours with a concentration of 300 μM CoCl2, followed by the administration of colchicine at a concentration of 1 μM after the ischemia treatment. The expression levels of NLRP3, TGF-β, and α-SMA were assessed using flow cytometry, and the data were analyzed through one-way ANOVA. Results: Administration of colchicine for 24 hours following ischemia resulted in a significant decrease in the relative levels of NLRP3, TGF-β, and α-SMA (p&lt;0.05) compared to the ischemia group. Conclusions: In vitro administration of colchicine can reduce post-ischemic remodeling, including the NLRP3 inflammasome, TGF-β, and α-SMA.

Analysis of the unicentric registry of the Infarction Code program: retrospective cohort

Acute coronary syndrome (ACS) is the most serious manifestation of coronary heart disease. The Infarction Code (according to its initialism in Spanish, CI: Código Infarto) program aims to improve the care of these patients. To describe the clinical presentation and outcomes of CI program in a coronary care unit (CCU). A database of a CCU with 5 years of consecutive records was analyzed. Patients diagnosed with ACS were included. The groups with acute myocardial infarction with and without ST-segment elevation were compared using Student's t, Mann-Whitney U and chi-squared tests. We calculated the relative risk (RR) and 95% confidence intervals (95% CI) of cardiovascular risk factors for mortality. A total of 4678 subjects were analyzed, 78.7% men, mean age 63 years (± 10.7). 80.76% presented acute myocardial infarction with positive ST-segment elevation and fibrinolytic was granted in 60.8% of cases. Percutaneous coronary intervention was performed in 81.4% of patients, which was successful in 82.5% of events. Patients classified as CI presented mortality of 6.8% vs. 11.7%, p = 0.001. Invasive mechanical ventilation had an RR of 26.58 (95% CI: 20.61-34.3) and circulatory shock an RR of 20.86 (95% CI: 16.16-26.93). The CI program decreased mortality by 4.9%. Early fibrinolysis and successful coronary angiography are protective factors for mortality within CCU.

Biological Signaling Network in Myocardial Infarction in Young Adults. A Study of Transcriptome Analysis

Background: Myocardial infarction (MI) is the common manifestation of coronary heart disease that develops from occlusion of coronary arteries. Several risk factors of MI were identified, but data pertaining to genetics and molecular mechanisms involved in the development of MI is limited. Therefore, the present study attempts to analyze the peripheral blood transcriptome information of MI patients and unveil the key genes involved in the pathogenesis of MI. Methods: Total RNA was extracted from the blood sample for illumine sequencing, and raw data obtained were subjected to quality control (QC) using the FastQC tool, followed by trimming of raw data by the fastp tool. Further processed high-quality data were aligned onto the human reference genome using HISAT2 aligner. Gene quantification was done using the feature Counts plugin in the subread package. The raw read counts were given as input to the differential expression analysis (DESeq2) R package for the computation of differentially expressed genes. Gene set enrichment analysis for gene ontology was done using the clusterProfiler R package. Results: A total of 609 genes were significantly expressed in the present study, of which 561 genes were upregulated and 48 genes were downregulated. This study presents overall changes in genes involved in different categories such as biological processes, molecular functions, and cellular components in responses to MI. Conclusions: The significantly deregulated genes identified in the present study not only indicate the molecular and cellular changes but also suggest the scope for the detection of specific gene markers for MI.

Lipoprotein(a) and Low-Molecular-Weight Apo(a) Phenotype as Determinants of New Cardiovascular Events in Patients with Premature Coronary Heart Disease.

Lipoprotein(a) (Lp(a)) is a genetic risk factor of atherosclerotic cardiovascular diseases (ASCVDs). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is related to vascular inflammation and detected in atherosclerotic plaques. A temporary increase in the circulating concentration of PCSK9 and Lp(a) was shown in patients with myocardial infarction (MI). The aim of this study was to evaluate the role of the apo(a) phenotype and the Lp(a) concentration as well as its complex with PCSK9 in the development of cardiac events and MI in patients with a premature manifestation of coronary heart disease (CHD). In a prospective study with retrospective data collection, we included 116 patients with premature CHD who were followed for a median of 14 years. The medical history and information on cardiovascular events after an initial exam as well as data on the levels of lipids, Lp(a), PCSK9, PCSK9-Lp(a) complex, and apo(a) phenotype were obtained. The patients were divided into two groups depending on the presence of a low- (LMW, n = 52) or high-molecular weight (HMW, n = 64) apo(a) phenotype. LMW apo(a) phenotype (odds ratio 2.3 (1.1 to 4.8), p = 0.03), but not elevated Lp(a) (1.9 (0.8-4.6), p = 0.13), was an independent predictor for the development of MI after adjustment for sex, age of CHD debut, initial lipids levels, and lipid-lowering treatment. The apo(a) phenotype also determined the relationship between Lp(a) and PCSK9 concentrations. The level of the PCSK9-Lp(a) complex was higher in LMW apo(a) patients. The LMW apo(a) phenotype is a risk factor for non-fatal MI in a long-term prospective follow-up of patients with premature CHD, and this link could be mediated via PCSK9.

Lipoprotein(A) and the age of manifestation of coronary heart disease

Lipoprotein(A) and the age of manifestation of coronary heart disease

The microvascular bed of the skin of lower limbs in patients with intermittent lameness and coronary heart disease as a possible model of their myocardial microcirculation

Purpose: to assess possibility to extrapolate findings of skin microvascular bed examination in lower extremities with laser Doppler flowmetry in patients with obliterating atherosclerosis as a model of their myocardial microcirculation in coronary heart disease.Material and methods. Males with angiographically confirmed coronary heart disease (n = 70) and obliterating atherosclerosis in lower limbarteries (n = 74) were taken in the study. Microcirculation of the skin in the left forearm in the Zakharyin – Head zone in patients with coronaryheart disease and skin microcirculation in the foot of affected limb in patients with obliterating atherosclerosis of arteries of lower extremities were examined with laser Doppler flowmetry. The basal blood flow, amplitude-frequency spectrum of its oscillations, myogenic, neurogenic vascular tone and occlusion parameters were assessed as well. Comparison groups included 50 practically healthy males for the patients with coronary heart disease and 20 males – for the patients with obliterating atherosclerosis of arteries of lower extremities. Patients were examinedat the initial stage and in 2–3 weeks after endovascular restoration of blood flow in the myocardium and lower limbs.Results and discussion. At the initial research stage, the microcirculation picture in patients with coronary heart disease and obliterating ath-erosclerosis in lower extremities differed from that of healthy individuals by shifts covering all links of the microvascular bed and characterizedby constriction of the precapillary segment, a statistically significant decrease in median values of capillary blood flow by 17.5 and 43.1 %,microvascular blood flow reserve – by 11.2 and 31.0 %, as well as by the increase in arteriolovenular blood bypass – by 10.3 and 70.8 %,respectively. After the restoration of blood flow in lower extremities in patients with obliterating atherosclerosis, muscular pain disappeared,and the ankle-shoulder index got normalized. At the same time, one could observe a statistically significant increase in the capillary blood flow(+13.6 %), the increase of reserve potential in microvascular bed (+20.6 %) with the simultaneous decrease of vascular tone in the precapillarysegment (–15.1 %) and of the blood bypass index (–25.0 %). Better clinical picture after coronary angioplasty in patients with coronary heart disease was accompanied with a similar and unidirectional tendency to positive changes in the microvascular bed.Conclusion. As far as etiopathogenetic mechanisms and clinical manifestations of coronary heart disease and obliterating atherosclerosis in arteries of lower extremities have much in common and microcirculatory shifts in forearm and foot skin in these patients before and after angioplasty are unidirectional, all these allow to suggest that one can see similar changes in the myocardium microcirculatory system in patients with coronary heart disease. Thus, it opens possibilities to have a targeted medicamentous impact at the microvascular level.

Metabolic changes of glycerophospholipids during the reparative phase after myocardial infarction injury.

Myocardial infarction (MI) is a fatal manifestation of coronary heart disease, and its underlying mechanism is still largely unknown. Lipid levels and composition alterations predict the risk of MI complications. Glycerophospholipids (GPLs) are important bioactive lipids and play a crucial role in the development of cardiovascular diseases. However, the metabolic changes in the GPLs profile during post-MI injury remain unknown. In the current study, we constructed a classic MI model by ligating the left anterior descending branch and assessed the alterations in both plasma and myocardial GPLs profiles during the reparative phase post-MI by liquid chromatography-tandem mass spectrometry analysis. We found that myocardial GPLs, but not plasma GPLs, were markedly changed after MI injury. Importantly, MI injury is associated with decreased phosphatidylserine (PS) levels. Consistently, the expression of phosphatidylserine synthase 1 (PSS1), which catalyzes the formation of PS from its substrate phosphatidylcholine, was significantly reduced in heart tissues after MI injury. Furthermore, oxygen-glucose deprivation (OGD) inhibited PSS1 expression and reduced PS levels in primary neonatal rat cardiomyocytes, while overexpression of PSS1 restored the inhibition of PSS1 and the reduction in PS levels caused by OGD. Moreover, overexpression of PSS1 abrogated, whereas knockdown of PSS1 aggravated, OGD-induced cardiomyocyte apoptosis. Our findings revealed that GPLs metabolism was involved in the reparative phase post-MI, and cardiac decreased PS levels, resulting from inhibition of PSS1, are important contributor to the reparative phase post-MI. PSS1 overexpression represents a promising therapeutic strategy to attenuate MI injury.

Seeking the culprit in a patient presented with lateral ST elevation myocardial infarction

ST Segment Elevation Myocardial Infarction (STEMI) is a frequent manifestation of coronary heart disease (CAD). The standard medical practice in centers equipped with a heart catheterization laboratory involves performing an immediate coronary angiogram with angioplasty of the responsible lesion. This case report describes a patient with lateral STEMI where identification of the culprit lesion causing the myocardial infarction was challenging. However, after meticulous examination of the coronary angiography, the lesion was detected, and the patient was treated with stent implantation, resulting in an uneventful recovery. Therefore, in cases of STEMI with an indistinct culprit lesion, careful investigation of the coronary angiography may offer a solution to the problem.

Identification of Key Genes and Biological Pathways Related to Myocardial Infarction through Integrated Bioinformatics Analysis.

Coronary heart disease is the leading cause of death worldwide. Myocardial infarction (MI) is a fatal manifestation of coronary heart disease, which can present as sudden death. Although the molecular mechanisms of coronary heart disease are still unknown, global gene expression profiling is regarded as a useful approach for deciphering the pathophysiology of this disease and subsequent diseases. This study used a bioinformatics analysis approach to better understand the molecular mechanisms underlying coronary heart disease. This experimental study was conducted in the department of cardiology, Aja University of Medical Sciences (2021-2022), Tehran, Iran. To identify the key deregulated genes and pathways in coronary heart disease, an integrative approach was used by merging three gene expression datasets, including GSE19339, GSE66360, and GSE29111, into a single matrix. The t test was used for the statistical analysis, with a significance level of P<0.05. The limma package in R was used to identify a total of 133 DEGs, consisting of 124 upregulated and nine downregulated genes. KDM5D, EIF1AY, and CCL20 are among the top upregulated genes. Moreover, the interleukin 17 (IL-17) signaling pathway and four other signaling pathways were identified as the potent underlying pathogenesis of both coronary artery disease (CAD) and MI using a systems biology approach. Accordingly, these findings can provide expression signatures and potential biomarkers in CAD and MI pathophysiology, which can contribute to both diagnosis and therapeutic purposes. Five signaling pathways were introduced in MI and CAD that were primarily involved in inflammation, including the IL-17 signaling pathway, TNF signaling pathway, toll-like receptor signaling pathway, C-type lectin receptor signaling pathway, and rheumatoid arthritis signaling pathway.

MiR-223 and MiR-186 Are Associated with Long-Term Mortality after Myocardial Infarction.

Background—The identification and stratification of patients at risk of fatal outcomes after myocardial infarction (MI) is of considerable interest to guide secondary prevention therapies. Currently, no accurate biomarkers are available to identify subjects who are at risk of suffering acute manifestations of coronary heart disease as well as to predict adverse events after MI. Non-coding circulating microRNAs (miRNAs) have been proposed as novel diagnostic and prognostic biomarkers in cardiovascular diseases. The aims of the study were to investigate the clinical value of a panel of circulating miRNAs as accurate biomarkers associated with MI and mortality risk prediction in patients with documented MI. Methods and Results—seven circulating plasma miRNAs were analyzed in 67 MI patients and 80 control subjects at a high cardiovascular risk but without known coronary diseases. Multivariate logistic regression analyses demonstrated that six miRNAs were independently associated with MI occurrence. Among them, miR-223 and miR-186 reliably predicted long-term mortality in MI patients, in particular miR-223 (HR 1.57 per one-unit increase, p = 0.02), after left ventricular ejection fraction (LVEF) adjustment. Kaplan–Meier survival analyses provided a predictive threshold value of miR-223 expression (p = 0.028) for long-term mortality. Conclusions—Circulating miR-223 and miR-186 are promising predictive biomarkers for long-term mortality after MI.

IGM autoantibodies against atherogenic lipoproteins and early manifestation of coronary heart disease

IGM autoantibodies against atherogenic lipoproteins and early manifestation of coronary heart disease

Long‐Term Cardioprotective Potential of Exogenous Ubiquitin in Myocardial Ischemia/Reperfusion Injury

BackgroundCoronary heart disease (CHD) is a leading cause of death worldwide. Myocardial ischemia/reperfusion (I/R) injury is a clinical manifestation of CHD. Timely reperfusion of coronary vessels in an ischemic injury is essential to limit the infarct size. However, reperfusion itself can induce cardiac cell death, and lead to increased adverse remodeling after an I/R injury. Previously, our lab has shown that pretreatment with ubiquitin (UB; a highly evolutionarily conserved protein) decreases inflammatory response and preserves heart function 3 days post‐I/R. The objective of this study is to investigate the long‐term cardioprotective potential of UB post‐I/R. To enhance the clinical relevance, UB treatment was started at the time of reperfusion. It is hypothesized that UB treatment has long‐term cardioprotective potential, improves cardiac function, and attenuates cardiac remodeling post injury.MethodsC57BL/6 male mice underwent ligation of the left anterior descending coronary artery (LCA) for 45 min. Mice were then treated with UB (1 µg/g body weight, i.p. injection) or saline at time of reperfusion of LCA. Sham animals underwent the same surgery without the ligation of LCA. Mice were treated with UB or saline twice/day (i.p. injections) for 3 days followed by treatment with UB (1 μg/g/h)or saline using micro‐osmotic pumps for 28 days. Heart function was measured at 3, 7, 14 and 28 days post‐I/R using echocardiography. Mice were sacrificed at 28 days post‐I/R. Left ventricular (LV) tissue was used to measure remodeling parameters and serum samples were used to measure a panel of 23 cytokines/chemokines using multiplex assay.ResultsI/R+saline group exhibited a significant reduction in heart function as observed by decreased percent fractional shortening (%FS) and percent ejection fraction (%EF) vs sham (p&lt;0.05) at 3, 7, 14 and 28 days post‐I/R. However, I/R+UB group showed significantly higher %FS and %EF vs I/R+saline (p&lt;0.05) throughout the observation period. Increases in fibrosis (measured by trichrome staining), myocyte apoptosis (measured using TUNEL assay), and hypertrophy (measured using WGA staining) were significantly lower in I/R+UB vs I/R+saline (p&lt;0.05). Expression of MMP‐2 and TIMP‐4 was lower, while expression of MMP‐9 (active) was significantly higher in I/R+UB vs I/R+saline (p&lt;0.05). Serum levels of IL‐6, IL‐2 and G‐CSF were significantly lower in I/R+UB vs I/R+saline (p&lt;0.05).ConclusionPost‐ischemic UB treatment improves heart function, and associates with decreased myocardial remodeling parameters (fibrosis, apoptosis, and hypertrophy) as well as decreased serum cytokines/chemokines levels.

Electroacupuncture at PC6 (Neiguan) Attenuates Angina Pectoris in Rats with Myocardial Ischemia-Reperfusion Injury Through Regulating the Alternative Splicing of the Major Inhibitory Neurotransmitter Receptor GABRG2.

Angina pectoris is the most common manifestation of coronary heart disease, causing suffering in patients. Electroacupuncture at PC6 can effectively alleviate angina by regulating the expression of genes, whether the alternative splicing (AS) of genes is affected by acupuncture is still unknown. We established a rat model of myocardial ischemia-reperfusion by coronary artery ligation and confirmed electroacupuncture alleviated the abnormal discharge caused by angina pectoris measured in EMG electromyograms. Analysis of the GSE61840 dataset established that AS events were altered after I/R and regulated by electroacupuncture. I/R decreased the expression of splicing factor Nova1 while electroacupuncture rescued it. Further experiments in dorsal root ganglion cells showed Nova1 regulated the AS of the GABRG2, specifically on its exon 9 where an important phosphorylation site is present. In vivo, results also showed that electroacupuncture can restore AS of GABRG2. Our results proved that electroacupuncture alleviates angina results by regulating alternative splicing.

Coronary Artery Calcium for Risk Stratification of Sudden Cardiac Death: The Coronary Artery Calcium Consortium

BackgroundCoronary artery calcium (CAC) is a marker of plaque burden. Whether CAC improves risk stratification for incident sudden cardiac death (SCD) beyond atherosclerotic cardiovascular disease (ASCVD) risk factors is unknown. ObjectivesSCD is a common initial manifestation of coronary heart disease (CHD); however, SCD risk prediction remains elusive. MethodsThe authors studied 66,636 primary prevention patients from the CAC Consortium. Multivariable competing risks regression and C-statistics were used to assess the association between CAC and SCD, adjusting for demographics and traditional risk factors. ResultsThe mean age was 54.4 years, 33% were women, 11% were of non-White ethnicity, and 55% had CAC >0. A total of 211 SCD events (0.3%) were observed during a median follow-up of 10.6 years, 91% occurring among those with baseline CAC >0. Compared with CAC = 0, there was a stepwise higher risk (P trend < 0.001) in SCD for CAC 100 to 399 (subdistribution hazard ratio [SHR]: 2.8; 95% CI: 1.6-5.0), CAC 400 to 999 (SHR: 4.0; 95% CI: 2.2-7.3), and CAC >1,000 (SHR: 4.9; 95% CI: 2.6-9.9). CAC provided incremental improvements in the C-statistic for the prediction of SCD among individuals with a 10-year risk <7.5% (ΔC-statistic = +0.046; P = 0.02) and 7.5% to 20% (ΔC-statistic = +0.069; P = 0.003), which were larger when compared with persons with a 10-year risk >20% (ΔC-statistic = +0.01; P = 0.54). ConclusionsHigher CAC burden strongly associates with incident SCD beyond traditional risk factors, particularly among primary prevention patients with low-intermediate risk. SCD risk stratification can be useful in the early stages of CHD through the measurement of CAC, identifying patients most likely to benefit from further downstream testing.

Correlation Between Troponin I Levels and Electrolytes of Sodium and Potassium in Acute Coronary Syndrome Patients at Budhi Asih Hospital

Acute Coronary Syndrome (ACS) is one of the clinical manifestations of coronary heart disease that most often causes of death. A sensitive laboratory examination to assess the presence of signs of myocardial infarction such as troponin I is used to diagnose ACS. Electrolyte levels can also be impaired in myocardial infarction. Electrolyte imbalance in the blood can affect the conduction and contractility of the heart, especially sodium and potassium which are needed to produce activation of the heart muscle. The aim of this study was to determine the correlation between troponin I levels and sodium and potassium levels of serum in acute coronary syndrome patients with diabetes mellitus. The research design was used a cross sectional analytical observation with secondary data. This study was used the Spearman correlation test with an alpha value of 0.05. The data were taken from the medical records section of Budhi Asih Hospital. The samples were used 65 data of patients. The results showed that there was a correlation between troponin I levels and sodium with a p value 0.001 (p &lt; 0.05), getting a fairly strong closeness level (r = -0.390) and negative direction. Likewise, the levels of troponin I with potassium showed a p value 0.000 (p &lt; 0.05), getting a fairly strong level of closeness (r = -0.487) and a negative direction. From this study, it can be concluded that there was a relationship between troponin I levels with sodium and potassium with a negative correlation direction which indicates that the higher troponin I levels, so the lower the sodium and potassium levels. Electrolyte examination, especially sodium and potassium, is important to help diagnose acute coronary syndrome in knowing the balance of body fluids so as to prevent death.