Coronary Heart Disease Pathology Research Articles

Competing Endogenous RNA Regulatory Networks of hsa_circ_0126672 in Pathophysiology of Coronary Heart Disease.

Coronary heart disease (CHD) is a global health concern, and its molecular origin is not fully elucidated. Dysregulation of ncRNAs has been linked to many metabolic and infectious diseases. This study aimed to explore the role of circRNAs in the pathogenesis of CHD and predicted a candidate circRNA that could be targeted for therapeutic approaches to the disease. circRNAs associated with CHD were identified and CHD gene expression profiles were obtained, and analyzed with GEO2R. In addition, differentially expressed miRNA target genes (miR-DEGs) were identified and subjected to functional enrichment analysis. Networks of circRNA/miRNA/mRNA and the miRNA/affected pathways were constructed. Furthermore, a miRNA/mRNA homology study was performed. We identified that hsa_circ_0126672 was strongly associated with the CHD pathology by competing for endogenous RNA (ceRNA) mechanisms. hsa_circ_0126672 characteristically sponges miR-145-5p, miR-186-5p, miR-548c-3p, miR-7-5p, miR-495-3p, miR-203a-3p, and miR-21. Up-regulation of has_circ_0126672 affected various CHD-related cellular functions, such as atherosclerosis, JAK/STAT, and Apelin signaling pathways. Our results also revealed a perfect and stable interaction for the hybrid of miR-145-5p with NOS1 and RPS6KB1. Finally, miR-145-5p had the highest degree of interaction with the validated small molecules. Henchashsa_circ_0126672 and target miRNAs, notably miR-145-5p, could be good candidates for the diagnosis and therapeutic approaches to CHD.

Systematic analysis of long non-coding RNA and mRNA expression changes in ApoE-deficient mice during atherosclerosis

Atherosclerosis plays an important role in the pathology of coronary heart disease, cerebrovascular disease, and systemic vascular disease. Long non-coding RNAs (lncRNAs) are involved in most biological processes and are deregulated in many human diseases. However, the expression alteration and precise role of lncRNAs during atherosclerosis are unknown. We report here the systematic profiling of lncRNAs and mRNAs in an ApoE-deficient (ApoE−/−) mouse model of atherosclerosis. Clariom D solutions for the mouse Affymetrix Gene Chip were employed to analyze the RNAs from control and ApoE−/− mice. The functions of the differentially expressed mRNAs and lncRNAs and the relationships of their expression with atherosclerosis were analyzed by gene ontology, co-expression network, pathway enrichment, and lncRNA target pathway network analyses. Quantitative real-time PCR (QRT-PCR) was used to determine the expression of mRNAs and lncRNAs. A total of 2212 differentially expressed lncRNAs were identified in ApoE−/− mice, including 1186 up-regulated and 1026 down-regulated lncRNAs (|FC| ≥ 1.1, p < 0.05). A total of 1190 differentially expressed mRNAs were found in the ApoE−/− mice with 384 up-regulated and 806 down-regulated (|FC| ≥ 1.1, p < 0.05). Bioinformatics analyses demonstrated extensive co-expression of lncRNAs and mRNAs and concomitant deregulation of multiple signaling pathways associated with the initiation and progression of atherosclerosis. The identified differentially expressed mRNAs and lncRNAs as well as the related signaling pathways may provide systematic information for understanding the pathogenesis and identifying biomarkers for the diagnosis, treatment, and prognosis of atherosclerosis.

Peripheral arterial stenosis and coronary artery disease coincidence

Atherosclerosis is a chronic slow-developing condition affecting medium-size and large blood vessels. It is the principal underlying pathology of coronary heart disease and stroke. In some countries, coronary artery disease (CAD) is the cause of nearly half (48%) of the deaths and, loss of productivity life. Peripheral arterial disease (PAD) is defined as atherosclerosis in peripheral arteries instead of coronary arteries. CAD and PAD have same risk factors and underlying pathophysiological processes. Therefore, patient with CAD should be considered for PAD. Ankle brachial index (ABI), duplex sonography, and some other non-invasive techniques are recommended for PAD diagnosis in patients with the history of CAD. Pharmacotherapy, endovascular interventions, and surgical management could be chosen according to the patient’s situation. Cardiologists and general practitioners should consider PAD in a patient with CAD or DM as a strong correlated disease.

Modern and advanced APPLICATION of echocardiography TOGETHER with tissue Doppler sonography in assessMENT OF structural and functional state of THE myocardium in patients with combined pathology of coronary heart disease and TYPE 2 diabetes mellitus (literature review)

The review contains information about the application of echocardiography together with tissue Doppler sonography in the assessment of structural and functional state of the myocardium in patients with combined pathology of coronary heart disease and type 2 diabetes mellitus. We have analyzed the latest achievements in noninvasive diagnostics of atherosclerotic process of coronary arteries, which makes it possible to diagnose the disease at a subclinical level. The article presents up-to-date possibilities and prospects of the application of tissue Doppler method in early diagnosis of coronary atherosclerosis in patients with diabetes.

Camphene, a Plant-Derived Monoterpene, Reduces Plasma Cholesterol and Triglycerides in Hyperlipidemic Rats Independently of HMG-CoA Reductase Activity

BackgroundCentral to the pathology of coronary heart disease is the accumulation of lipids, cholesterol and triglycerides, within the intima of arterial blood vessels. The search for drugs to treat dislipidemia, remains a major pharmaceutical focus. In this study, we evaluated the hypolipidemic properties of the essential oil from Chios mastic gum (MGO).Methodology/Principal FindingsThe hypolipidemic effect of MGO was investigated in naïve as well as in rats susceptible to detergent-induced hyperlipidemia. Serum cholesterol and triglycerides were determined using commercial kits. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase activity was measured in HepG2 cell extracts using a radioactive assay; cellular cholesterol and cholesterol esters were assessed using gas chromatography. MGO administration into naïve rats resulted in a dose-dependent reduction in the constitutive synthesis of serum cholesterol and triglycerides. In hyperlipidemic rats, MGO treatment had also a strong hypolipidemic effect. By testing various components of MGO, we show for the first time that the hypolipidemic action is associated with camphene. Administration of camphene at a dose of 30 µg/gr of body weight in hyperlipidemic rats resulted in a 54.5% reduction of total cholesterol (p<0.001), 54% of Low Density Lipoprotein (LDL)-cholesterol (p<0.001) and 34.5% of triglycerides (p<0.001). Treatment of HepG2 cells with camphene led to a decrease in cellular cholesterol content to the same extend as mevinolin, a known HMG-CoA reductase inhibitor. The hypolipidemic action of camphene is independent of HMG-CoA reductase activity, suggesting that its hypocholesterolemic and hypotriglyceridemic effects are associated with a mechanism of action different than that of statins.ConclusionsGiven the critical role that the control of hyperlipidemia plays in cardiovascular disease, the results of our study provide insights into the use of camphene as an alternative lipid lowering agent and merits further evaluation.

Does interleukin-18 or tumour necrosis factor-α have an independent association with the risk of coronary heart disease? Results from a prospective study in New Zealand

Background: The pro-inflammatory cytokines, interleukin (IL)-18 and tumour necrosis factor-α (TNFα) may play a role in coronary heart disease (CHD). We aimed to extend data on their relationships to the risk of CHD in generally healthy populations. Methods: During 5.5 years follow-up in the Fletcher Challenge general population cohort there were 256 CHD cases, and 615 controls were matched for age and sex. Baseline plasma levels of IL-18 and TNFα were related to CHD risk in available samples (77%). Results: Plasma levels of IL-18 (11% increase in mean, p = 0.01) and TNFα (10% increase in mean p = 0.024) were significantly elevated in CHD cases versus controls. In univariable models IL-18 was associated with CHD risk (odds ratio [OR] upper third to lower third, 1.63; 95% CI 1.08, 2.46), but TNFα was not (OR 1.33; 95% CI 0.87, 2.02).After adjusting for major CHD risk factors and CRP, the association of IL-18 with CHD risk was attenuated (OR 1.69; 95% CI 0.94, 3.03). Conclusions: IL-18, but not TNFα, had a non-negligible association with CHD risk, although the association of IL-18 with risk was weak after full adjustment. These cytokines may play a role in CHD pathology, but may not be robust risk biomarkers.

Role of NOD2/CARD15 in coronary heart disease.

Background:Bacterial DNA has been repeatedly detected in atheromatous lesions of coronary heart disease (CHD) patients. Phylogenetic signatures in the atheroma lesions that are similar to those of bacterial biofilms on human barrier organs, including the respiratory or gastrointestinal tract, raise the question of a defective barrier function in CHD. NOD2 plays a major role in defense against bacterial invasion. Genetic variation in the CARD15 gene, which encodes NOD2, was previously shown to result in a barrier defect that causes chronic inflammatory disorders (e.g. Crohn disease). In the present study, we investigated the possible involvement of NOD2/CARD15 in the pathology of CHD by i) analyzing the local expression of NOD2 in atherectomy versus healthy tissue (n = 5 each) using histochemical immunofluorescence and ii) by testing the three major functional CARD15 variants (R702W, G908R and 1007fs) for association with early-onset CHD in 900 German patients and 632 healthy controls.Results:In atherectomy tissue of CHD patients, NOD2 was detected in inflammatory cells at the luminal sides of the lesions. However, the allele and genotype frequencies of the three major CARD15 polymorphisms did not differ between CHD patients and controls.Conclusion:The NOD2 up-regulation in atheroma lesions indicates an involvement of this protein in the pathology of CHD. Although NOD2 could be important in local immune response mechanisms, none of the analyzed CARD15 variants seem to play a significant role in the etiology of CHD.

Cardiovascular disease--linking pathology and epidemiology.

Coronary heart disease (CHD) in the form of myocardial infarction first came to attention early in the 20th century. Mortality from CHD increased dramatically after the First World War and had assumed epidemic proportions, particularly in the USA, by 1945. The ensuing research stemmed almost exclusively from the lipid infiltration hypothesis for atheroma. Using epidemiological methods, pathological evidence for the thrombotic component of CHD was demonstrated by Morris as early as 1951. Morris's main work was based, first, on routine autopsy records at the London (now Royal London) Hospital and, second, on the National Necropsy Survey relating physical activity at work to pathological findings. The indications from Morris's work that thrombosis contributes as much to clinical CHD as atheroma were in due course strengthened by the findings of clinical trials of aspirin, prospective studies incorporating measures of haemostatic function and further studies of pathology. Recognition of the thrombotic contribution to CHD does not materially alter approaches to prevention through lifestyle modifications but does have major implications for pharmacological measures. Thus, aspirin and thrombolytic therapy are mandatory in the acute stage of suspected myocardial infarction while aspirin is also part of accepted practice in the longer term in secondary prevention. The value of warfarin is being rediscovered, often at a lower and therefore safer intensity of anticoagulation than previously considered necessary. The effect that warfarin may have on the vessel wall as well as on occlusion of the lumen is helping to reconcile the two major hypotheses for the pathology of CHD. Much of our current knowledge about the origins, management and prevention of CHD stems from Morris's early studies linking pathology and epidemiology.