Examining the effects of coronary artery disease- and mitochondrial biogenesis-related genes' and microRNAs' expression levels on metabolic disorders in epicardial adipose tissue.

BACKGROUND AND AIMS: Epicardial adipose tissue (EAT) surrounds the heart and coronary arteries and is important for comprehending the pathogenesis of coronary artery disease (CAD). We aimed to evaluate the expressions of mitochondrial biogenesis- and CAD-related genes and miRNAs in EAT by comparing them to visceral adipose tissue (VAT) in CAD, diabetes, and obesity subgroups. METHODS: In this study, a total of 93 individuals were recruited, and EAT samples (63 CAD; 30 non-CAD) and VAT samples from 65 individuals (46 CAD; 19 non-CAD) were collected. For further analysis, the study population was divided according to obesity and diabetes status. PRKAA1, PPARGC1A, SIRT1, RELA, TNFA, and miR-155-5p, let-7g-5p, miR-1247-5p, miR-326 expression levels were examined. RESULTS: PRKAA1 and let-7g-5p were differentially expressed in EAT compared to VAT. TNFA expression was upregulated significantly in both tissues of CAD patients. In EAT, PRKAA1, PPARGC1A, and SIRT1 were downregulated with diabetes. Moreover, PPARGC1A expression is decreased under the condition of obesity in both tissues. EAT expressions of miR-1247-5p and miR-326 were downregulated with obesity, while miR-155-5p is decreased only in the VAT of obese. Also, miRNAs and genes were correlated with biochemical parameters and each other in EAT and VAT (p < 0.050). CONCLUSIONS: The findings demonstrating distinct let-7g-5p and AMPKα1 mRNA expression between EAT and VAT underscores the importance of tissue-specific regulation in different clinical outcomes. In addition, the differential expressions of investigated genes and miRNAs highlight their responsiveness to obesity, DM, and CAD in adipose tissues.

[Effect of Mitochondrial Dysfunction on Coronary Artery Disease - Part 2]. / Mitokondriyal Disfonksiyonun Koroner Arter Hastal������ ��zerine Etkisi - B��l��m II.

Organelles whose functions change as a result of molecular processes are involved in the pathogenesis of atherosclerosis, which is the main cause of coronary artery disease, in addition to molecular processes. Recently, the role of mitochondria in the pathogenesis of coronary artery disease has attracted the attention of researchers. Mitochondria is a cell organelle with its own genome that plays a regulatory role in aerobic respiration, energy production, and cell metabolism. The number of mitochondria in cells changes dynamically, and there are di���erent numbers of mitochondria in every tissue and every cell, depending on their function and energy needs. Oxidative stress causes mitochondrial dysfunction by leading to alterations in the mitochondrial genome and mitochondrial biogenesis. The dysfunctional mitochondria population in the cardiovascular system is closely related to the coronary artery disease process and cell death mechanisms. It is thought that the altered mitochondria (dys)function accompanying the molecular changes in the atherosclerosis process will be among the new therapeutic targets of coronary artery disease in the near future.

[Genetic Evaluation of Mitochondria Dysfunction in Coronary Artery Disease: Part 1]. / Koroner Arter Hastaliginda Mitokondri Islev Bozuklugunun Genetik Açidan Incelenmesi: Bölüm 1.

Mitochondria are cell organelles that play an important role in various cellular processes, especially in aerobic respiration and energy production. Although it has its own genome, the mitochondrial genome does not encode all of the proteins necessary for the mitochondria to function. Nuclear genome is needed for increased mitochondrial number, metabolic activities associated with mitochondria, and replication of mitochondrial deoxyribonucleic acid. As a result of mitochondria dysfunction in cells, oxidative stress occurs with the formation of reactive oxygen species, a product of oxidative metabolism, and the oxidant/antioxidant imbalance. Reactive oxygen species damage cellular molecules such as proteins, ribonucleic acid, deoxyribonucleic acid, and mitochondrial deoxyribonucleic acid under the conditions of oxidative stress. Molecular changes as a result of the reactive oxygen species cause the loss of mitochondria function, resulting in an increased number of dysfunctional mitochondria. Thus, the loss of function of mitochondria and defects in oxidative metabolism increase the formation of reactive oxygen species and cause an increase in mutations in mitochondrial deoxyribonucleic acid. These results also affect mitochondrial biogenesis and accelerate the formation of multifactorial diseases as a result of the decrease in the number of functional mitochondria. In addition, microribonucleic acids, one of the epigenetic regulators, regulate nuclear and mitochondrial genes that control mitochondrial functions. Mitochondrial deoxyribonucleic acid mutated with reactive oxygen species, altered nuclear genome regulators and micro-ribonucleic acids, have been associated with various diseases mediated by mitochondrial dysfunction, including aging and coronary artery disease.

Cities can benefit from complex supply chains.

Supply chain complexity is perceived to exacerbate the supply disruptions or shocks experienced by a city. Here, we calculate two network measures of supply chain complexity based on the relative number-horizontal complexity-and relative strength-vertical complexity-of a city's suppliers. Using a large dataset of more than 1 million annual supply flows to 69 major cities in the United States for 2012-2015, we show that a trade-off pattern between horizontal and vertical complexity tends to characterize the architecture of urban supply networks. This architecture shapes the resistance of cities to supply chain shocks. We find that a city experiences less intense shocks, on average, as supplier relative diversity (horizontal complexity) increases for more technologically sophisticated products, which may serve as a mechanism for buffering cities against supply chain shocks. These results could help cities anticipate and manage their supply chain risks.

Examining the effects of the CLU and APOE polymorphisms' combination on coronary artery disease complexed with type 2 diabetes mellitus.

AIMS: Coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) are important and increasing public health problems. This study aimed to identify the impact of APOE and CLU gene polymorphisms on the prevalence of both diseases, along with the effect of these polymorphisms on lipid profile and glucose metabolism. METHODS: 736 CAD patients (≥50 stenosis) and 549 non-CAD subjects (≤30 stenosis) were genotyped for APOE (rs429358 and rs7412) and CLU (rs11136000) gene polymorphisms using hydrolysis probes in real-time PCR. Blood samples of the individuals were drawn before coronary angiography and biochemical analyses were done. The associations between the polymorphisms and the selected parameters were assessed using statistical analysis. RESULTS: In this study, the ε2 and ε4 isoforms of apoE were associated with serum lipid levels and TC/HDL-C and LDL-C/HDL-C ratios in analysis adjusted for several confounders and in crude analysis. It was observed that CLU T allele carrier non-CAD subjects had lower glycosylated hemoglobin levels. Furthermore, the effects of APOE and CLU polymorphisms were assessed on CAD and T2DM presence. In crude and multiple logistic regression analyses, the ε2 isoform carriers had a lower risk for CAD complexed with T2DM. When the combinational effects of APOE and CLU polymorphisms were examined, the ε2 and T allele carriers had decreased risk for CAD complexed with T2DM compared to non-carriers. CONCLUSIONS: In conclusion, the combination of APOE and CLU polymorphisms is associated with CAD-DM status along with the APOE ε2 isoform by itself, and the apoE isoforms are strongly associated with serum lipid levels.