Pathogenesis Of Ischemic Heart Disease Research Articles

In silico exploration of bioactive compounds from Acorus calamus L. for targeted treatment of ischemic heart disease: Molecular insights and therapeutic prospects

Abstract BACKGROUND: Ischemic heart disease (IHD) accounts for 80%–85% of mortality, highlighting the need to develop effective and noninvasive management strategies. Lekhana karma (therapeutic scrapping) helps in balancing the imbalanced Kapha and Medodhatu, which are important factors in the pathogenesis of IHD. Vacha—Acorus calamus Linn (AC) is 1 of the 10 Lekhaneeya drugs described in Charaka Samhita and is widely available and cost-effective. However, its bioactive phytoconstituents’ mode of action and molecular entities remain unexplored. Hence, this study aimed to elucidate the mode of action of its bioactive compounds and their interaction with IHD disease targets and pathways. METHODS: Phytochemicals from AC were collected, followed by screening of bioactive phytochemicals, collecting gene identifications, and pathways related to IHD. Later, common compounds and pathways were identified, and common targets between phytochemicals and pathways were sorted. A further network of phytochemicals-pathways-targets was constructed followed by molecular docking of highly enriched disease targets and phytochemicals. RESULTS: An in silico study revealed that 19 main active compounds of AC are interacting with 48 targets involved in regulating biological processes in the IHD. Molecular docking analyses were performed to explore the potential and affinity of these compounds with disease targets. Galangin, alpha-asarone, beta-asarone, and isoelemicin exhibited significant interactions with IHD disease targets, such as prostaglandin G/H synthase 2, cytochrome P450 1A2, transcription factor p65, vascular endothelial growth factor A, and tyrosine-protein kinase. Additionally, the study identified the interaction between the top 4 phytochemicals and the five most enriched disease targets. CONCLUSION: These findings provide a promising avenue for transforming bioactive phytoconstituents in AC into novel drug entities for treating IHD. The in silico approach identifies therapeutic targets, guides wet lab studies, and aids multi-compound management for IHD.

Plasma and platelets amino acids in coronary artery disease and atrial fibrillation patients – are they linked?

Introduction. The impact of circulating amino acid levels and their combinations on the pathogenesis of ischemic heart disease and atrial fibrillation is a current issue, otherwise, the platelets amino acid spectrum is still under discussion, despite the known pathogenetic role of platelets in these disorders. Aim. To compare changes in the plasma and platelets amino acid spectrum in patients with coronary artery disease and atrial fibrillation as well as to find their connections. Materials & Methods. 300 patients were divided into 3 groups: I group – 149 patients with coronary artery disease without arrhythmias, II group – 124 patients with coronary artery disease and atrial fibrillation paroxysm, and the control group – 27 patients without coronary artery disease and arrhythmias. Plasma and platelet amino acid levels were detected by means of ion exchange liquid column chromatography. Results & Conclusions. In platelets amino acid spectrum, a significant rise in leucine (12.63%), isoleucine (10.73%), and Fishers’ ratio (6.37%); a decrease in threonine (23.05%), valine (30.83%) levels, glycine (32.21%), serine (5.06%), and glycine+serine sum (20.51%) in group 2 patients was found compared with group 1, p<0.05. In the plasma amino acids spectrum, a significant increase in glutamate, branched-chain amino acids, and Fishers’ ratio and a decrease in glycine in group 2 patients was checked in comparison with group 1, p<0.05. Only 10 moderate strength correlations were revealed between the plasma and platelets amino acid spectrum of investigated patient’s groups. These changes in platelets and plasma amino acids spectrum were not significantly congruent in patients with coronary artery disease and atrial fibrillation. Plasma and platelets amino acid spectrum should be analyzed separately in patients with coronary artery disease and atrial fibrillation for further studies and evaluation of new prognostic markers and pathogenetic clues to their development. Keywords: myocardial ischemia, heart rhythm violations, proteins, metabolomics.

Unraveling the Molecular Mechanisms of Activated Protein C (APC) in Mitigating Reperfusion Injury and Cardiac Ischemia: a Promising Avenue for Novel Therapeutic Interventions.

Ischemic heart disease, which results from plaque formation in the coronary arteries, hinders the flow of oxygenated blood to the heart, leading to ischemia. Reperfusion injury remains a significant challenge for researchers, and the mechanisms underlying myocardial ischemia-reperfusion injury (MIRI) are not entirely understood. The review directs future research into potential targets in clinical treatment based on our present understanding of the pathophysiological mechanisms of MIRI. The study provides insights into the mechanisms underlying MIRI and offers direction for future research in this area. The use of targeted therapies may hold promise in improving cardiac function in the elderly and minimizing the adverse effects of revascularization therapies. The purpose of this review is to analyze the role of activated protein C (APC) in the pathogenesis of ischemic heart disease, heart failure, and myocardial ischemia-reperfusion injury, and discuss the potential of APC-based therapeutics.

Edgeworthia gardneri (Wall.) Meisn. extract protects against myocardial infarction by inhibiting NF-κB-and MAPK-mediated endothelial inflammation.

Experimental and clinical evidence has demonstrated a pivotal role of inflammation in the pathogenesis of ischemic heart disease, and targeting inflammation has been shown to provide clinical benefits for patients with coronary disease. Endothelial cells constitute the majority of non-cardiomyocytes in the heart. Endothelial pro-inflammatory activation is recognized as a critical component in the pathophysiology of cardiovascular disease. The dried flowers of Edgeworthia gardneri (Wall.) Meisn. (EG) have been widely used as Tibetan folk medicine to ameliorate a range of metabolic disorders, such as diabetes mellitus, hyperlipidemia, hypertension, and obesity. However, its role in modulating endothelial inflammation and ischemic heart disease has not been evaluated. Herein, using a preclinical rat model of coronary artery ligation-induced myocardial infarction (MI), we demonstrated that systemic administration of EG extract (EEEG) attenuated ischemic cardiac injury. EEEG reduced myocardial infarct size, improved cardiac function, and ameliorated adverse cardiac remodeling. Moreover, the cardioprotective effects of EEEG were associated with decreased MI-induced myocardial inflammation. Consistent with the anti-inflammatory role of EEEG in vivo, EEEG attenuated TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) activation and monocyte-endothelial cell firm adhesion in vitro. Mechanistically, our data showed that EEEG's mode of action suppresses the activation of NF-κB, ERK, and p38 MAPK signaling pathways in ECs. Importantly, we demonstrated that EEEG inhibits endothelial inflammation in an NF-κB- and p38 MAPK-dependent manner using pharmacological inhibitors. Collectively, this study identified EG as a potential therapeutic agent in attenuating endothelial inflammation and managing ischemic cardiovascular disease.

Alterations of Cardiac Protein Kinases in Cyclic Nucleotide-Dependent Signaling Pathways in Human Ischemic Heart Failure

ObjectivesImpaired protein kinase signaling is a hallmark of ischemic heart disease (IHD). Inadequate understanding of the pathological mechanisms limits the development of therapeutic approaches. We aimed to identify the key cardiac kinases and signaling pathways in patients with IHD with an effort to discover potential therapeutic strategies.MethodsCardiac kinase activity in IHD left ventricle (LV) and the related signaling pathways were investigated by kinomics, transcriptomics, proteomics, and integrated multi-omics approach.ResultsProtein kinase A (PKA) and protein kinase G (PKG) ranked on top in the activity shift among the cardiac kinases. In the IHD LVs, PKA activity decreased markedly compared with that of controls (62% reduction, p = 0.0034), whereas PKG activity remained stable, although the amount of PKG protein increased remarkably (65%, p = 0.003). mRNA levels of adenylate cyclases (ADCY 1, 3, 5, 9) and cAMP-hydrolysing phosphodiesterases (PDE4A, PDE4D) decreased significantly, although no statistically significant alterations were observed in that of PKGs (PRKG1 and PRKG2) and guanylate cyclases (GUCYs). The gene expression of natriuretic peptide CNP decreased remarkably, whereas those of BNP, ANP, and neprilysin increased significantly in the IHD LVs. Proteomics analysis revealed a significant reduction in protein levels of “Energy metabolism” and “Muscle contraction” in the patients. Multi-omics integration highlighted intracellular signaling by second messengers as the top enriched Reactome pathway.ConclusionThe deficiency in cAMP/PKA signaling pathway is strongly implicated in the pathogenesis of IHD. Natriuretic peptide CNP could be a potential therapeutic target for the modulation of cGMP/PKG signaling.

P200 ISCHEMIC HEART IN PAZIENTS UNDER 30: AN UNSOLVED CHELLENGE

Abstract Background The pathogenesis of ischemic heart disease (IHD) in young patients is still unclear. Several studies have demonstrated the existence of peculiar cardiovascular risk factors (CRFs) that differ from the typical factors involved in the more common IHD of adults.Plaque rupture represents the most common etiology of myocardial infarction (MI), nonetheless, other events can play a role in young patients affected by IHD, including coronary artery plaque erosion, coronary microvascular dysfunction, spontaneous dissection of the coronary artery, and coronary artery spasm secondary to drug abuse. Due to the differences in the clinical manifestations, diagnosis, and therapeutic management, further research is needed to study the profile of MI in young patients1 Clinical Case A 28–year–old male, occasional smoker, negative familiar anamnesis for IHD. His past medical history was significant for an acute coronary syndrome (ACS) STEMI at the age of 20 years old, treated with percutaneous transluminal coronary angioplasty (PTCA) with scaffold in the interventricular anterior artery (IVA). After 7 years he was admitted following a thrombotic occlusion of the IVA, managed with PTCA/ drug–eluting stent (DES) followed by coronary artery bypass surgery diverting the blood flow of the IVA in the left internal mammary artery (IMA). After only 11 months he presented with a new ACS NSTEMI treated with PTCA/DES of the IVA in the left IMA. No biochemical signs of coagulopathy or peripheral artery disease were disclosed, and the supra–aortic trunks resulted normal. Nevertheless, a significant increase in the blood levels of homocysteine and slightly elevated values of fibrinogen, D–dimers, and C–reactive protein. Erythrocyte sedimentation rate resulted within the physiological ranges. Discussion and Conclusion The peculiar medical history of the described patient suggests a marked tendency not only for the formation and plaque rupture but also for platelet aggregation. The only significant and persistent values that were found to be elevated were homocysteine and inflammatory markers. One–year follow–up examination revealed complete regression of the symptoms with double antiaggregating therapy and supplements of folic acid. The rarity of such cases should prompt new research to better understand IHD in this population and possible targeted treatments Acute Myocardial Infarction in Young Individuals; Rajiv Gulati; Mayo Clinic Proceedings, V 95, I. 1, P136–156, 2020.

The role of thrombin in the pathogenesis of atherosclerosis and its complications

Thrombin is a key regulator of the homeostasis system. Also, it actively participates in progression of various systemic diseases, including atherosclerosis. There is a large amount of experimental and clinical data on the involvement of thrombin in the pathogenesis of ischemic heart disease (IHD). Thus, studying thrombin activity regulation is promising. Also, the question whether it is possible to use biomarkers of thrombin activity as predictors of cardiovascular complications in IHD patients is relevant. The present review focuses on major mechanisms of thrombin functioning, its role in development and progression of atherosclerosis, and available tests for evaluation of thrombin functional activity. Major clinical studies are discussed that evaluated the efficacy of thrombin inhibitors and protease-activated receptor antagonists.

Sex Differences: Potential Impact in Vascular Physiopathology or Ischemic Heart Disease

Pathophysiological mechanisms for development and progression of ischemic heart disease, which is essentially an age-related condition, may differ between men and women. Age-related changes in cardiac and vascular anatomy and physiopathology combined with traditional risk factors affect the likelihood of developing heart disease. Sex specific features of cardiac and vascular remodeling with age are associated with a higher prevalence of ischemic heart disease in women post-menopause. Cardiac symptoms such as chest pain/discomfort are often less in women, which generally results in less aggressive clinical treatment compared to men. Incidentally, treatment guidelines for acute myocardial infarction have for the most part, been established from studies with a large male cohort. Sex differences relating to effects of ischemia on overall cardiovascular function could contribute to worse clinical outcomes for females. Treatment options for women also arise because they generally present with multiple co-morbidities. The present review focuses on recent findings for sex differences in pathogenesis of ischemic heart disease, vascular function as well as potential use of cardio protection strategies.

New Insights Into the Role of Mitochondria Quality Control in Ischemic Heart Disease.

IHD is a significant cause of mortality and morbidity worldwide. In the acute phase, it's demonstrated as myocardial infarction and ischemia-reperfusion injury, while in the chronic stage, the ischemic heart is mainly characterised by adverse myocardial remodelling. Although interventions such as thrombolysis and percutaneous coronary intervention could reduce the death risk of these patients, the underlying cellular and molecular mechanisms need more exploration. Mitochondria are crucial to maintain the physiological function of the heart. During IHD, mitochondrial dysfunction results in the pathogenesis of ischemic heart disease. Ischemia drives mitochondrial damage not only due to energy deprivation, but also to other aspects such as mitochondrial dynamics, mitochondria-related inflammation, etc. Given the critical roles of mitochondrial quality control in the pathological process of ischemic heart disease, in this review, we will summarise the efforts in targeting mitochondria (such as mitophagy, mtROS, and mitochondria-related inflammation) on IHD. In addition, we will briefly revisit the emerging therapeutic targets in this field.

The role of soluble leptin receptor in the pathogenesis of coronary heart disease

Introduction. The participation of soluble leptin receptor (SLR) in the formation of hyperleptinemia and leptin resistance in patients with coronary artery disease (CAD) in combination with obesity is discussed. Aim. Study of the role of SLR in the pathogenesis of ischemic heart disease. Materials and methods. A cohort study of 744 patients was performed: 465 patients with CAD (56 years old, Q1=44; Q3=62), 270 patients without CAD (52 years old, Q1=44; Q3=56). Methods: EchoCG, heart computed tomography, coronary angiography. In the blood serum, the lipids, glucose, creatinine, uric acid, and c-reactive protein were assessed using a highly sensitive method (HF-CRP). Concentrations of SLR, leptin (LN), adiponectin (total and high molecular weight), fatty acid binding protein-4 (FABP-4) tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), serum insulin were determined by enzyme immunoassay. Results. The level of SLR in blood serum in men and women with CAD is lower than in men without CAD (p <0.001). In CAD patients, obesity was associated with a low SLR level in the blood serum and a high free LN index. At a serum SLR concentration of <7.5ng/ml in men with CAD, the incidence of obesity was higher simultaneously with signs of visceral obesity of the heart, the presence of atherosclerotic plaques in the common carotid arteries, high glycaemic levels, insulin, IL-6, and LN in serum, serum LN/adiponectin ratio and a high HOMA-IR index. Diabetes mellitus, visceral obesity, high levels of hs-CRP, TNF-α, FABP-4, serum insulin, and HOMA-IR index were more often detected in women with coronary artery disease with SLR <10.2 ng/ml. In men and women with CAD, there were no differences in SLR concentration depending on the extent of coronary atherosclerosis. Conclusion. An increase in the free LN index indicates the disruption of connections in the leptin-receptor system and reflects the mechanisms of compensation for overcoming the resistance of peripheral tissues to leptin, which is confirmed by a noticeable negative relationship between the levels of SLR and leptin in the serum of men with coronary artery disease. A low concentration of SLR in patients with CAD is associated with obesity, pro-atherogenic and pro-inflammatory markers of cardiovascular diseases.

Matrix metalloproteinase-2 and angiotensin-1 gene polymorphisms in patient who have coronary artery disease

Introduction: The rupture of atherosclerotic plaques is caused by the impact of matrix metalloproteinases (MMPs) upon the local fibrous valve and so might convert a chronic disease to a myocardial infarction, ultimately leading to instant death. Angiotensin converting enzyme (ACE) is actively engaged in the pathogenesis of ischemic heart disease. This study tries to unravel whether/how ACE and MMP-2 gene polymorphism contributes to the occurrence of Coronary Artery Disease (CAD). Materials and methods: A total of 300 individuals (100 healthy/200 patients) were included in the study. A PCR-RFLP method was utilized for ACE gene I/D and DNA sequencing MMP-2 (-1306 C/T) polymorphisms. Results: The ACE-1 gene D/D, I/D and I/I genotype frequency of the CAD cohort was 50%, 29%, and 21%, respectively whereas that of the healthy control cohort was 37%, 45% and 18%, respectively. Our findings indicate that the groups differed significantly in relation to the ACE-1 genotypes (p=0.021). The frequencies of ACE-1 gene allele I and D in both cohorts did not reveal a significant difference (p=0.314). In addition, the two groups did not manifest MMP-2 (rs243865) gene polymorphism. Conclusion: The association between MMP-2 gene polymorphism and CAD is too weak to suggest a conclusive evidence. The I/D genotype frequency remained higher in the healthy individuals than in the CAD cohort, while in the CAD group D/D genotype was more frequently than control group. Finally, the patients with D/D genotype tend to bear greater risk for cardiovascular diseases.

From Brain to Heart: Possible Role of Amyloid-β in Ischemic Heart Disease and Ischemia-Reperfusion Injury

Ischemic heart disease (IHD) is among the leading causes of death in developed countries. Its pathological origin is traced back to coronary atherosclerosis, a lipid-driven immuno-inflammatory disease of the arteries that leads to multifocal plaque development. The primary clinical manifestation of IHD is acute myocardial infarction (AMI),) whose prognosis is ameliorated with optimal timing of revascularization. Paradoxically, myocardium re-perfusion can be detrimental because of ischemia-reperfusion injury (IRI), an oxidative-driven process that damages other organs. Amyloid-β (Aβ) plays a physiological role in the central nervous system (CNS). Alterations in its synthesis, concentration and clearance have been connected to several pathologies, such as Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA). Aβ has been suggested to play a role in the pathogenesis of IHD and cerebral IRI. The purpose of this review is to summarize what is known about the pathological role of Aβ in the CNS; starting from this evidence, we will illustrate the role played by Aβ in the development of coronary atherosclerosis and its possible implications in the pathophysiology of IHD and myocardial IRI. Better elucidation of Aβ’s contribution to the molecular pathways underlying IHD and IRI could be of great help in developing new therapeutic strategies.

A unique proteomic signature of extracellular vesicles derived from mesenchymal stromal cells of epicardial fat from patients with and without ischemic heart disease

Abstract Background Mesenchymal stromal cells (MSCs) have been implicated in the development and progression of myocardial diseases. However, the role of extracellular vesicles (EVs) secreted from human MSCs (hMSCs) of epicardial fat (eFat) in the pathogenesis of ischemic heart disease (IHD) has never been studied. Purpose We sought to characterize EVs from eFat-hMSCs of patients with and without IHD. Methods We collected eFat specimens from 12 patients with (n=7) and without (n=5) IHD who underwent open heart surgery. We isolated and cultured hMSCs by enzymatic digestion and adherence to plastic. EVs were separated from the culture media by differential ultra-centrifugation. We assessed EV size and structure by electron microscopy and nanoparticle tracking analysis. Finally, we evaluated the proteomic profile of EVs from ischemic and non-ischemic patients by mass spectrometry. Results eFat-hMSCs from ischemic patients, secreted higher amounts of small EVs (size range of 70–200 nm) compared with non-ischemic controls (Figure 1A+B). Proteomic analysis revealed over 1,000 proteins inside isolated EVs. We identified 13 proteins that were significantly differentially expressed between patients with and without IHD, including apolipoprotein E, transforming growth factor-β and collagen α-1 (Figure 1C). We performed an enrichment analysis which showed that EVs from eFat-hMSCs from ischemic patients encapsulated functional protein networks associated with immune activation. Unlike IHD patients, EVs from non-ischemic patients carried functional protein networks that regulate angiogenesis. Conclusions eFat-hMSCs of patients with IHD secrete higher amounts of small EVs with a unique proteomic signature related to immune activation. EVs derived from eFat-hMSCs should be further studied for their potential role in the initiation and progression of cardiovascular diseases, such as coronary artery disease, heart failure and arrhythmias. Figure 1 Funding Acknowledgement Type of funding source: None

Thrombin generation's role in predicting coronary disease severity.

BackgroundThrombin, a key enzyme of the clotting system, is involved in thrombus formation, platelet activation, and atherosclerosis, thereby possessing a central role in the pathogenesis of ischemic heart disease. Studies have shown an association between thrombin generation (TG) and cardiovascular morbidity and mortality, but results have been equivocal. Our aim was to study the predictive ability of TG assay in evaluating coronary stenosis severity.MethodsIn this prospective study we recruited patients with acute coronary syndrome (ACS) or acute chest pain (without evidence of myocardial injury) planned for coronary angiography. Thrombin generation was evaluated by Calibrated Automated Thrombogram (CAT) prior to angiography. Primary end points were significant coronary stenosis and the Syntax I score evaluated by coronary angiography.ResultsFrom April 2018 through September 2019, we recruited 128 patients. In the primary analysis there was no significant association between TG and significant coronary stenosis nor between TG and syntax I score, however, there was a positive correlation between peak height and troponin peak (Spearman correlation coefficient 0.194, P-value = 0.035). In sub-group analysis, the chest pain group bare no association between TG and coronary stenosis. In unstable angina group there was an association between peak height and significant coronary stenosis (P-value = 0.029), and in non ST-elevation myocardial infarction group, TG values possessed a relatively good predictive ability of significant coronary stenosis (area under the receiver operating characteristic curve of ~65%) and a positive correlation between both lag time and ttpeak with the syntax I score was noticed (Spearman correlation coefficient 0.31, P-value = 0.099 and Spearman correlation coefficient 0.37, P-value = 0.045 respectively).ConclusionIn patients with acute chest pain, TG values, evaluated by CAT, do not predict severity of coronary stenosis, nor do they possess prognostic value. Yet, in ACS patients, TG may have the ability to predict coronary disease severity.

Modulatory Effects of Chinese Herbal Medicines on Energy Metabolism in Ischemic Heart Diseases.

Ischemic heart disease (IHD), a major global public health problem, is associated with high morbidity and mortality. Although the very best of modern approaches have proven effective in reducing morbidity and mortality, the poor prognosis of patients with IHD remains a major clinical concern. Cardiac energy metabolism is increasingly recognized as having a role in the pathogenesis of IHD, inducing metabolic substrate alterations, mitochondrial dysfunction, impaired function of the mitochondrial electron transport chain, and deprivation of cardiac energy. Factors involved in cardiac energy metabolism provide potential therapeutic targets for the treatment of IHD. Chinese herbal medicines (CHMs) have a long history of use in the prevention and treatment of cardiovascular diseases with multi-component, multi-target, and multi-signaling. Increasing evidence suggests that Chinese herbal medicines may improve myocardial ischemia through modulating cardiac energy metabolism. Here, we describe the possible targets and pathways of cardiac energy metabolism for CHMs, and appraise the modulatory effects of CHMs on energy metabolism in IHD. Especially, this review focuses on summarizing the metabolic effects and the underlying mechanisms of Chinese herbal medicines (including herbs, major bioactive components, and formulas) in IHD. In addition, we also discuss the current limitations and the major challenges for research investigating the use of CHMs in the treatment of cardiovascular diseases.

Malondialdehyde and its role in pathogenesis of unstable forms of ischemic heart disease

Lipid peroxidation plays a major role in cellular biology and, consequently, in all physiological and pathophysiological processes. Malondialdehyde (MDA) is a well-studied product of lipid peroxidation. MDA is a toxic substance, which is synthesized during arachidonic acid peroxidation. This substance can react with nucleic acids, phospholipids, cholesterol and proteins, having proatherogenic and cancerogenic effects. Oxidative stress, including some biochemical reactions of MDA, plays a major role in pathogenesis of ischemic heart disease (IHD). Nevertheless, determination of oxidative stress activity is not widely used in clinical practice, because it is expensive, controversial and non-specific. Increase of MDA above 100 pmol/ml is considered a prognostic biomarker of IHD course and carotid atherosclerosis, but practical usage of this marker needs further analysis of oxidation processes with other pathogenetic mechanisms of IHD. The purpose of this study is to estimate MDA concentration and its pathogenetic role according to correlation analysis in patients with acute forms of IHD. We analyzed data of 20 inpatients with IHD, unstable angina pectoris, which were assessed and treated according to actual guidelines and other documents. Results were statistically processed with the help of Spearman’s correlation analysis. In patients with IHD, unstable angina pectoris the mean MDA value was slightly increased (122.52 pmol/ml) and characterized by the significant range (in 1.7 times). In patients with MDA level higher than mediana we noticed higher levels of segmented neutrophils and proinflammatory neutrophil / limphocyte ratio, lower relative levels of lymphocytes and monocytes and 3.75 higher odds ratio for having bilirubin lower than 10 pmol/ml, which is also a criterion of oxidative stress. When MDA level was normal, it was significantly associated with monocytes number (r=0.92) and high density lipoproteins concentration (r=-0.79). In case of increased MDA level it correlated with band neutrophils (r=0.77), thickness of left ventricle posterior wall and interventricular septum (r=-0.79 and r=-0.79). Malondialdehyde is not only a marker of oxidative stress, but also a marker of inflammation activation, dyslipidemia, carbohydrate intolerance, thrombosis, arterial hypertension and tachycardia. Keywords: malondialdehyde, ischemic heart disease, oxidative stress, inflammation, structural heart parameters.

Evaluation of Therapeutic Agents Targeting the Pathogenesis of Coronary Artery Spasm: A Mini Review.

Coronary artery spasm (CAS) plays an important role in the pathogenesis of ischemic heart disease. The clinical manifestations of CAS include variant angina, myocardial infarction and sudden death. Although endothelial dysfunction and hyperreactivity of vascular smooth muscle cells have been associated with CAS, the underlying mechanisms remain unclear. Thus, there is a long way to go to truly understand the pathogenesis of CAS to formulate effective treatments. This article discusses the pathophysiological mechanisms as well as downstream molecular pathways of CAS, with a focus on potential therapeutic targets.

Advances in the Application of Fondaparinux in Acute Coronary Syndrome

Acute Coronary Syndrome (ACS) is one of the major causes of death worldwide, including unstable angina, ST-segment elevation myocardial infarction and NST-segment elevation myocardial infarction. ACS refers to a series of life-threatening heart diseases, which is caused by rupturing coronary plaque and releasing thrombin activation. Then thrombin is activated and generates plaque and thrombosis, which increases the risk of cardiac death and myocardial infarction. Aggressive and conservative treatment is available in clinic practice. Anticoagulant therapy is usually the first choice for conservative treatment and used in combination with dual antiplatelet drugs, which plays an important role in the treatment of acute coronary syndrome. Fondaparinux as a commonly used anticoagulant drug is both antithrombotic effectively and can reduce the risk of bleeding and coronary microvascular dysfunction in the pathogenesis of ischemic heart disease. However, it increased the rate of bleeding. People pay more attention to the role of long-term prognosis. Domestic and foreign researches contrast outcomes of acute coronary syndrome of fondaparinux and low molecular weight heparin.

Downregulation of miR-200a protects cardiomyocyte against apoptosis

Background/aimsAcute myocardial infarction (AMI) is a major clinical manifestation of ischemic heart disease and represents a significant cause of morbidity and mortality. However, key regulators in the pathogenesis of ischemic heart disease remain controversial. The present study was designed to investigate the involvement of miR-200a and its related mechanism in AMI. MethodsLeft coronary artery (LCA) ligation was conducted to induce an AMI mouse model. The infarct size was measured by TTC staining. H2O2 was used to induce an AMI model in vitro. miR-200a mimics, anti-miR-200a antisense oligodeoxyribonucleotides (AMO-200a), as well as corresponding negative controls were transfected into cardiomyocytes to observe the effect of miR-200a. Flow cytometry was used to detect cell apoptosis. Real-time PCR, immunofluorescence and western blot assays were used to evaluate gene expression at RNA or protein levels, respectively. ResultsApoptosis was activated in AMI models. The expression of miR-200a was upregulated both in the peri-infarcted region of mice myocardium and H2O2-treated cardiomyocytes. The co-administration of AMO-200a decreased the number of apoptosis cells and altered the expression of apoptosis related proteins. Interestingly, bioinformatics analysis results revealed that miR-200a could bind to the 3′-untranslated regions (3’-UTR) of Fus mRNA. In addition, the expression of Fus was downregulated in the AMI mouse models and in H2O2-treated cardiomyocytes. The alteration of miR-200a negatively regulated Fus expression in cardiomyocytes. Also, the protective effect of AMO-200a was observed through its regulation of Fus. ConclusionMiR-200a-dependent apoptosis signaling pathway plays an important role in the pathogenesis of AMI injury and could be an exciting potential therapeutic target.

A Breakthrough in the Pathogenesis of Ischemic Heart Disease: the MINOCA and INOCA Challenge

Classical coronary syndromes as angina pectoris, ischemiaand myocardial infarction, which were describedmany years ago, are generally attributed tothe presence of different degrees of coronary arteryobstruction caused by atherosclerotic plaques.Atherosclerosis is a chronic inflammatory diseaseaffecting both sexes that starts in childhood, and evenin intrauterine life, and progresses throughoutthe years, especially in subjects with cardiovascularrisk factors. In this inflammatory process, and in thepresence of a specific or inadequate metabolic environments,such as diabetes mellitus or those resultingfrom traditional risk factors, β-lipoproteins and glycatedproteins oxidize becoming antigenic and causingendothelial dysfunction. This favors the penetrationof these molecules into vascular subendotheliallayers where they generate an immunogenic reaction,activating monocytes that are transformed into macrophages,which, together with other cells involved inthis process, create a lipid inflammatory core. Vascularsmooth muscle cells, recruited by inflammation,change from a contractile phenotype to a secretoryphenotype and generate collagen, which surroundsthe lipid inflammatory core and promotes calciumdeposition, completing the formation of the atheromatousplaque. This complex process (briefly describedhere) involves a multitude of molecules thatare produced as a result of oxidation, inflammation,apoptosis, angiogenesis, degradation of the fibrouscap, influx of red cells, tissue factor expression andother components that determine the progression ofthe atherosclerotic plaque over time.