Abstract P005: Mitochondrial Dysfunction in Heart of Coronary Artery Disease: Correlation with Telomerase Activity

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Karima Ait-Aissa ◽  
Joohwan Kim ◽  
Garrett Morgan ◽  
Janine H Santos ◽  
Amadou K Camara ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Critical Role ◽  
Telomerase Activity ◽  
Dominant Negative ◽  
Pcr Analysis ◽  
Tissue Samples ◽  
Artery Disease

Rational: Heart disease is the leading cause of death worldwide and abnormalities in mitochondrial function are increasingly recognized in association with cardiomyopathy, heart failure, endothelial dysfunction and coronary artery disease (CAD). However the direct contribution and mechanism of the mitochondrial dysfunction on the development of CAD is not fully determined. We have recently shown a critical role of TERT, the catalytic subunit of telomerase, as a regulator of mitochondrial integrity in the microcirculation. We observed increased expression of the dominant negative splice variant of TERT ( β -del) in the Left Ventricle from subjects with CAD. Therefore, we hypothesize that TERT ( β -del) decreases mitochondrial telomerase activity in the human heart resulting in mitochondrial damage that contributes to an environment that promotes the development of CAD . Methods: Fresh and frozen tissue samples of discarded heart tissue from subjects with and without CAD were used. Protein, cell lysate or mitochondria were isolated using standard techniques. Mitochondrial DNA, levels of NAD+ and ATP as well as mitochondrial oxidative phosphorylation were evaluated. Results: PCR analysis revealed an increased frequency of mitochondrial common deletion, an established marker for mitochondrial abnormalities (0.9±0.2 in CAD; vs 1.5±0.2 in non-CAD; N=8; P<0.05). NAD+ and ATP levels were significantly decreased in CAD subjects compared to non-CAD (291±62 and 0.5±0.1 RLU/mg protein in CAD vs. 4203±336 and 84.1±24.8 pmol/mg protein in non-CAD respectively; N=15; P<0.005). Decrease respiration control index (RCI) in the presence of either complex I substrate K (+)-pyruvate/malate (PM) or complex II substrate K (+)-succinate (SUC) was observed in tissue form subjects with CAD (KPM-RCI: 2.9±1.3; SUC-RCI: 7.6± 1.9 in CAD vs KPM-RCI: 8.5±1.9; SUC-RCI: 19.1± 8.3 in non-CAD; N=3; P<0.05) Conclusions: Together these results point to significantly impaired mitochondrial function in subjects with CAD that are associated with decreased in mitochondrial telomerase activity.

Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

2019 ◽  
Vol 133 (22) ◽  
pp. 2283-2299
Author(s):  
Apabrita Ayan Das ◽  
Devasmita Chakravarty ◽  
Debmalya Bhunia ◽  
Surajit Ghosh ◽  
Prakash C. Mandal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Chronic Inflammation ◽  
Ex Vivo ◽  
Human Subjects ◽  
Critical Role ◽  
Atherosclerotic Cardiovascular Disease ◽  
Tnf Α ◽  
Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

Mitochondrial Dysfunction Induced by Statin Contributes to Endothelial Dysfunction in Patients with Coronary Artery Disease

2010 ◽  
Vol 10 (2) ◽  
pp. 130-138 ◽  
Author(s):  
Yuk-Ling Dai ◽  
Ting-Hin Luk ◽  
Chung-Wah Siu ◽  
Kai-Hang Yiu ◽  
Hiu-Ting Chan ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Endothelial Dysfunction ◽  
Mitochondrial Dysfunction ◽  
Artery Disease

scholarly journals UGT1A1 rs4148323 A Allele is Associated With Increased 2-Hydroxy Atorvastatin Formation and Higher Death Risk in Chinese Patients With Coronary Artery Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
He-Ping Lei ◽  
Min Qin ◽  
Li-Yun Cai ◽  
Hong Wu ◽  
Lan Tang ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Ultra Performance Liquid Chromatography ◽  
Chinese Patients ◽  
Tissue Samples ◽  
Human Liver Tissue ◽  
Death Risk ◽  
Risk Of Death ◽  
Increased Risk ◽  
Artery Disease

It is widely accepted that genetic polymorphisms impact atorvastatin (ATV) metabolism, clinical efficacy, and adverse events. The objectives of this study were to identify novel genetic variants influencing ATV metabolism and outcomes in Chinese patients with coronary artery disease (CAD). A total of 1079 CAD patients were enrolled and followed for 5 years. DNA from the blood and human liver tissue samples were genotyped using either Global Screening Array-24 v1.0 BeadChip or HumanOmniZhongHua-8 BeadChip. Concentrations of ATV and its metabolites in plasma and liver samples were determined using a verified ultra-performance liquid chromatography mass spectrometry (UPLC-MS/MS) method. The patients carrying A allele for the rs4148323 polymorphism (UGT1A1) showed an increase in 2-hydroxy ATV/ATV ratio (p = 1.69E−07, false discovery rate [FDR] = 8.66E−03) relative to the value in individuals without the variant allele. The result was further validated by an independent cohort comprising an additional 222 CAD patients (p = 1.08E−07). Moreover, the rs4148323 A allele was associated with an increased risk of death (hazard ratio [HR] 1.774; 95% confidence interval [CI], 1.031–3.052; p = 0.0198). In conclusion, our results suggested that the UGT1A1 rs4148323 A allele was associated with increased 2-hydroxy ATV formation and was a significant death risk factor in Chinese patients with CAD.

scholarly journals Role of Multi-Detector CT Angiography in Assesmente of Athrosclerotic Coronary Artery Disease

2020 ◽  
Vol 15 (2) ◽  
pp. 40-44
Author(s):  
Mustafa Adham Ismael
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Arteries ◽  
Critical Role ◽  
Diagnostic Technique ◽  
Arterial Grafts ◽  
Cross Sectional ◽  
Venous Grafts ◽  
Artery Disease

Background:  Imaging has a critical role in the diagnosis and evaluation of cardiac diseases, beginning with chest radiography and fluoro-scopy and progressing to coronary angio-graphy, echocardiography, nuclear medicine and recently  multidetector computed tomo-graphy (MDCT) as well as magnetic resonance (MR) imaging Objective: To highlight the role of Multi-detector CT in the evaluation of coronary artery disease and its importance of being noninvasive diagnostic technique. Methods: A cross sectional study for 20 patients. Patients were asked to fast 6 hours prior to the examination and the patients with heart rates above 65 beats per minute were given cardio-selective beta-blocker and for heart rate above 75 (up to 85) beat/min, the best systole phase was used for reconstructing our images Results: for Evaluation of native coronary arteries, the CTCA showed significant lesions (occlusion or >60 % stenosis) in the native arteries of 13 patients and insignificant lesions in 7 patients.       Evaluation of CABG (8 arterial grafts); for (LIMA) graft, 83% were patented,   and 17% were narrowed and 100 % of (radial graft) were   patent. For Venous Grafts the study included 10 venous grafts; 70 % were patent, 20% were narrowed and 10 % were totally occluded. Conclusion: The multi-slice CTCA is now a clinically reliable noninvasive tool that allows the evaluation of the native coronary arteries, the bypass grafts, coronary stents.

scholarly journals Acyl-CoA: cholesterol acyltransferases-2 gene polymorphism is associated with increased susceptibility to coronary artery disease in Uygur population in Xinjiang, China

2019 ◽  
Vol 39 (2) ◽  
Author(s):  
Yong-Tao Wang ◽  
Buamina Maitusong ◽  
Yi-Tong Ma ◽  
Zhen-Yan Fu ◽  
Yi-Ning Yang ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Critical Role ◽  
Fatty Acyl ◽  
Primary Objective ◽  
Cholesterol Homeostasis ◽  
Dominant Model ◽  
Nucleotide Polymorphisms ◽  
Increased Risk ◽  
Artery Disease

Abstract Background: Acyl-CoA: cholesterol acyltransferases (ACAT) is the only enzyme that catalyzes the synthesis of cholesterol esters (CE) from free cholesterol and long-chain fatty acyl-CoA and plays a critical role in cellular cholesterol homeostasis. In the present study, our primary objective was to explore whether the single-nucleotide polymorphisms (SNPs) in ACAT-2 gene were associated with coronary artery disease (CAD) in Uygur subjects, in Xinjiang, China. Methods: We designed a case–control study including 516 CAD patients and 318 age- and sex-matched control subjects. Using the improved multiplex ligation detection reaction (iMLDR) method, we genotyped two SNPs (rs28765985 and rs7308390) of ACAT-2 gene in all subjects. Results: We found that the genotypes, the dominant model (CC + CT vs TT) and over-dominant model (CT vs CC + TT) of rs28765985 were significantly different between CAD patients and the controls (P=0.027, P=0.012 and P=0.035, respectively). The rs28765985 C allele was associated with a significantly elevated CAD risk [CC/CT vs TT: odds ratio (OR) = 1.48, 95% confidence interval (CI) = 1.02–2.16, P=0.04] after adjustment for confounders. The TC and LDL-C levels were significantly higher in rs28765985 CC/CT genotypes than that in TT genotypes (P<0.05). Conclusions: Rs28765985 of ACAT-2 gene are associated with CAD in Uygur subjects. Subjects with CC/CT genotype or C allele of rs28765985 were associated with an increased risk of CAD.

Cardiolipin Remodeling by ALCAT1 Links Hypoxia to Coronary Artery Disease by Promoting Mitochondrial Dysfunction

2021 ◽  
Author(s):  
Dandan Jia ◽  
Jun Zhang ◽  
Jia Nie ◽  
John-Paul Andersen ◽  
Samantha Rendon ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Mitochondrial Dysfunction ◽  
Artery Disease

Expression of Ubiquitin in Peripheral Inflammatory Cells from Patients with Coronary Artery Disease

2008 ◽  
Vol 36 (6) ◽  
pp. 1227-1234 ◽  
Author(s):  
S-M Chen ◽  
H-X Zhang ◽  
Y-G Li ◽  
D-M Wang ◽  
G-H Zhang ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Angina Pectoris ◽  
Critical Role ◽  
Inflammatory Cells ◽  
Ubiquitin Proteasome System ◽  
Stable Angina Pectoris ◽  
Protein Levels ◽  
Ubiquitin Proteasome ◽  
Artery Disease

In addition to its role in the removal of damaged and unneeded proteins, the ubiquitin–proteasome system (UPS) may play a key role in coronary artery disease (CAD). To investigate the expression of ubiquitin in monocytes and lymphocytes isolated from patients at different stages of CAD, 120 patients with CAD (40 with acute myocardial infarction [AMI], 40 with unstable angina pectoris [UAP] and 40 with stable angina pectoris [SAP]) were selected; 40 patients with normal coronary arteries served as controls. At both the mRNA and protein levels, ubiquitin expression was higher in patients with CAD than in controls, and patients with AMI had a much higher expression of ubiquitin (at both the mRNA and protein levels) than those with SAP and UAP. These data indicate that ubiquitin expression increased with increasing severity of CAD, suggesting that ubiquitin may play a critical role in the development and progression of CAD.

P4502Noninvasively assessed mitochondrial function estimated by skin fluorescence is abnormal in coronary artery disease

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Rechcinski ◽  
U Cieslik-Guerra ◽  
P Siedlecki ◽  
E Trzos ◽  
K Wierzbowska-Drabik ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Mitochondrial Function ◽  
Augmentation Index ◽  
Cholesterol Concentration ◽  
Apnea Hypopnea Index ◽  
Entire Group ◽  
Skin Fluorescence ◽  
Artery Disease ◽  
Hyperemic Response

Abstract Mitochondrial NADH undergoes oxygenation to NAD+ and NADH molecules, activated by ultraviolet light, start to emit fluorescence at a wavelength 460nm. This phenomenon can be measured to non-invasively assess mitochondrial function in the forearm epidermis at rest, during transient ischaemia, and afterward reperfusion assuming that it reflects abnormal microvascular circulation. We hypothesized that flow-dependent skin fluorescence (FDSF) is abnormal in patients with coronary atherosclerosis. Methods Prototype device manufactured by Angionica (Poland) was used to quantify FDSF recorded in forearm before, during and after 100 s of brachial artery occlusion in 63 individuals (26 with coronary artery disease (CAD) and 37 healthy volunteers. The absolute value of baseline FDSF (BASE), maximum FDSF (MAX), minimal FDSF (MIN), percentage ischemic response (IR) and hyperemic response (HR) were measured. Age, lipid profile, fasting glucose, HbA1c, C-reactive protein (CRP), systolic and diastolic blood pressure, pulse wave velocity (PWV), augmentation index, time domain heart rate variability parameters (SDNN, rMSSD) and estimated apnea/hypopnea index -eAHI (Holter ECG based), BMI, intima-media thickness (IMT), left ventricle systolic and diastolic function were determined in all study participants to search for potential correlations with FDSF. Results Measurements were feasible in all study subjects and examination duration was 9±1min. Hyperemic response (HR) was significantly lower in patients with CAD vs controls: 10,4 vs. 14,36 vs 14,73 – p=0,025. Other parameters: BASE, MAX, MIN, and IR were not significantly different between groups (p>0,05). In the entire group, HR was correlated with age (r=−0,23 p=0,037), and with total or LDL cholesterol (r=0,37 p=0,001 and r=0,36 p=0,001). Interestingly, HR was also positively correlated with SDNN (r=0,26 p=0,044) and rMSSD (r=0,29 p=0,026). Mode of FDSF examination Conclusion Abnormal mitochondrial function probably secondary to microcirculatory disorder is detectable by noninvasive skin fluorescence test as decreased hyperemic response in patients with coronary disease. Age and cholesterol concentration as well as autonomic balance Holter indices are correlated with hyperemic response. Acknowledgement/Funding POIR.01.01.01.0540/15-00

scholarly journals Comparative Proteome Analysis of Epicardial and Subcutaneous Adipose Tissues from Patients with or without Coronary Artery Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Yu xing Zhao ◽  
Hui juan Zhu ◽  
Hui Pan ◽  
Xue mei Liu ◽  
Lin jie Wang ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Mitochondrial Dysfunction ◽  
Differentially Expressed ◽  
Signal Pathways ◽  
Differentially Expressed Proteins ◽  
Absolute Quantitation ◽  
Adipose Tissues ◽  
Artery Disease ◽  
Subcutaneous Adipose

Background and Aims. Owing to its unique anatomical structure and metabolism, epicardial adipose tissue (EAT) has attracted amount of attention in coronary artery disease (CAD) research. Here, we analyzed differences in proteome composition in epicardial (EAT) and subcutaneous adipose tissues (SAT) from patients with or without CAD. Methods. EAT and SAT samples were collected from 6 CAD patients and 6 non-CAD patients. Isobaric Tagging for Relative and Absolute Quantitation (iTRAQ) analysis combined with liquid chromatography tandem-mass spectrometry (LC-MS/MS) was performed to identify the differentially expressed proteins. Results. In total, 2348 proteins expressed in EAT and 2347 proteins expressed in SAT were separately identified. 385 differentially expressed proteins were found in EAT and 210 proteins were found in SAT in CAD patients compared to non-CAD patients. Many proteins differentially expressed in EAT of CAD patients were involved in biological functions associated with CAD development such as cell-to-cell signaling and interaction, inflammatory response, and lipid metabolism. Differential expressions of proteins (MMP9, S100A9, and clusterin) in EAT or SAT were involved in several signaling pathways such as mitochondrial dysfunction, acute phase inflammation, and LXR/RXR activation, which was confirmed by western blotting, and similar results were obtained. Conclusions. The largest profiles of differentially expressed proteins in EAT and SAT between CAD patients and non-CAD patients were identified. The significant signal pathways, mitochondrial dysfunction, and LXR/RXR activation, which differential proteins were involved in, were firstly found to play roles in EAT of CAD patients, and clusterin was firstly found to be upregulated in EAT of CAD patients.

Sign in / Sign up

Export Citation Format

Share Document