Proteomic approach to coronary atherosclerosis shows ferritin light chain as a significant marker: evidence consistent with iron hypothesis in atherosclerosis

2003 ◽  
Vol 13 (1) ◽  
pp. 25-30 ◽  
Author(s):  
Sun-Ah You ◽  
Stephen R. Archacki ◽  
George Angheloiu ◽  
Christine S. Moravec ◽  
Shaoqi Rao ◽  
...  

Coronary artery disease (CAD) is the leading cause of mortality and morbidity in developed nations. We hypothesized that CAD is associated with distinct patterns of protein expression in the coronary arteries, and we have begun to employ proteomics to identify differentially expressed proteins in diseased coronary arteries. Two-dimensional (2-D) gel electrophoresis of proteins and subsequent mass spectrometric analysis identified the ferritin light chain as differentially expressed between 10 coronary arteries from patients with CAD and 7 coronary arteries from normal individuals. Western blot analysis indicated significantly increased expression of the ferritin light chain in the diseased coronary arteries (1.41 vs. 0.75; P = 0.01). Quantitative real-time PCR analysis showed that expression of ferritin light chain mRNA was decreased in diseased tissues (0.70 vs. 1.17; P = 0.013), suggesting that increased expression of ferritin light chain in CAD coronary arteries may be related to increased protein stability or upregulation of expression at the posttranscriptional level in the diseased tissues. Ferritin light chain protein mediates storage of iron in cells. We speculate that increased expression of the ferritin light chain may contribute to pathogenesis of CAD by modulating oxidation of lipids within the vessel wall through the generation of reactive oxygen species. Our results provide in situ proteomic evidence consistent with the “iron hypothesis,” which proposes an association between excessive iron storage and a high risk of CAD. However, it is also possible that the increased ferritin expression in diseased coronary arteries is a consequence, rather than a cause, of CAD.

2003 ◽  
Vol 15 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Stephen R. Archacki ◽  
George Angheloiu ◽  
Xiao-Li Tian ◽  
Fen Lai Tan ◽  
Nick DiPaola ◽  
...  

Genetic factors increase the risk to coronary artery disease (CAD). To date, a limited number of genes that potentially contribute to development of CAD have been identified. In this study, we have performed large-scale gene expression analysis of ∼12,000 human genes in nine severely atherosclerotic and six nonatherosclerotic human coronary arteries using oligonucleotide microarrays. Fifty-six genes showed differential expression in atherosclerotic coronary artery tissues; expression of 55 genes was increased in atherosclerotic coronary arteries, whereas only one gene, GST, encoding a reducing agent, showed downregulated expression. The expression data of selected genes were validated by quantitative RT-PCR analysis as well as immunostaining. The associations of 49 genes with CAD appear to be novel, and they include genes encoding ICAM-2, PIM-2, ECGF1, fusin, B cell activator ( BL34, GOS8), Rho GTPase activating protein-4, retinoic acid receptor responder, β2-arrestin, membrane aminopeptidase, cathepsins K and H, MIR-7, TNF-α-induced protein 2 (B94), and flavocytochrome 558. In conclusion, we have identified 56 genes whose expression is associated with CAD, and 49 of them may represent new genes linked to CAD.


2020 ◽  
pp. 5-10
Author(s):  
O. M. Korzh

Among the cardiovascular diseases associated with atherosclerosis, chronic coronary heart disease, including angina, is the most common form. It is the myocardium lesion that develops as a result of an imbalance between the coronary circulation and metabolic needs of heart muscle. The presence of angina symptoms often indicates a pronounced narrowing of one or more coronary arteries, but also occurs in non−obstructive arterial impairment and even in normal coronary arteries. Factors of functional damage to the coronary arteries are spasm, temporary platelet aggregation and intravascular thrombosis. Today there are opportunities not only to use the therapy with proven effectiveness, aimed at reducing the risk of complications, including fatal, but also to treat angina (ischemia), which improves the patient's life quality. The drug protocol includes the ones with a proven positive effect on this disease prognosis, which are mandatory if there are no direct contraindications to use, as well as a large group of antianginal or anti−ischemic drugs. The choice of a particular drug or its combinations with other drugs is carried out in accordance with generally accepted recommendations: taking into account the individual approach, the severity of angina, hemodynamic parameters (heart rate and blood pressure, presence of comorbid conditions). If drug therapy is ineffective, the option of coronary myocardial revascularization (percutaneous coronary angioplasty or coronary artery bypass grafting) is considered. Due to the high mortality and morbidity rates of coronary heart disease worldwide, one of the priorities of practical health care is the prevention of diseases caused by atherosclerosis. Key words: coronary heart disease, angina, family physician, prognosis, drug therapy.


2020 ◽  
Vol 26 ◽  
Author(s):  
Maria Bergami ◽  
Marialuisa Scarpone ◽  
Edina Cenko ◽  
Elisa Varotti ◽  
Peter Louis Amaduzzi ◽  
...  

: Subjects affected by ischemic heart disease with non-obstructive coronary arteries constitute a population that has received increasing attention over the past two decades. Since the first studies with coronary angiography, female patients have been reported to have non-obstructive coronary artery disease more frequently than their male counterparts, both in stable and acute clinical settings. Although traditionally considered a relatively infrequent and low-risk form of myocardial ischemia, its impact on clinical practice is undeniable, especially when it comes to infarction, where the prognosis is not as benign as previously assumed. Unfortunately, despite increasing awareness, there are still several questions left unanswered regarding diagnosis, risk stratification and treatment. The purpose of this review is to provide a state of the art and an update on current evidence available on gender differences in clinical characteristics, management and prognosis of ischemic heart disease with non-obstructive coronary arteries, both in the acute and stable clinical setting.


Author(s):  
Runlei Ma ◽  
Marly van Assen ◽  
Daan Ties ◽  
Gert Jan Pelgrim ◽  
Randy van Dijk ◽  
...  

Abstract Objectives To investigate the association of pericoronary adipose tissue mean attenuation (PCATMA) with coronary artery disease (CAD) characteristics on coronary computed tomography angiography (CCTA). Methods We retrospectively investigated 165 symptomatic patients who underwent third-generation dual-source CCTA at 70kVp: 93 with and 72 without CAD (204 arteries with plaque, 291 without plaque). CCTA was evaluated for presence and characteristics of CAD per artery. PCATMA was measured proximally and across the most severe stenosis. Patient-level, proximal PCATMA was defined as the mean of the proximal PCATMA of the three main coronary arteries. Analyses were performed on patient and vessel level. Results Mean proximal PCATMA was −96.2 ± 7.1 HU and −95.6 ± 7.8HU for patients with and without CAD (p = 0.644). In arteries with plaque, proximal and lesion-specific PCATMA was similar (−96.1 ± 9.6 HU, −95.9 ± 11.2 HU, p = 0.608). Lesion-specific PCATMA of arteries with plaque (−94.7 HU) differed from proximal PCATMA of arteries without plaque (−97.2 HU, p = 0.015). Minimal stenosis showed higher lesion-specific PCATMA (−94.0 HU) than severe stenosis (−98.5 HU, p = 0.030). Lesion-specific PCATMA of non-calcified, mixed, and calcified plaque was −96.5 HU, −94.6 HU, and −89.9 HU (p = 0.004). Vessel-based total plaque, lipid-rich necrotic core, and calcified plaque burden showed a very weak to moderate correlation with proximal PCATMA. Conclusions Lesion-specific PCATMA was higher in arteries with plaque than proximal PCATMA in arteries without plaque. Lesion-specific PCATMA was higher in non-calcified and mixed plaques compared to calcified plaques, and in minimal stenosis compared to severe; proximal PCATMA did not show these relationships. This suggests that lesion-specific PCATMA is related to plaque development and vulnerability. Key Points • In symptomatic patients undergoing CCTA at 70 kVp, PCATMAwas higher in coronary arteries with plaque than those without plaque. • PCATMAwas higher for non-calcified and mixed plaques compared to calcified plaques, and for minimal stenosis compared to severe stenosis. • In contrast to PCATMAmeasurement of the proximal vessels, lesion-specific PCATMAshowed clear relationships with plaque presence and stenosis degree.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Rong Zhang ◽  
Weitao Jiang ◽  
Xin Liu ◽  
Yanan Duan ◽  
Li Xiang ◽  
...  

Abstract Background Apple replant disease (ARD) has been reported from all major fruit-growing regions of the world, and is often caused by biotic factors (pathogen fungi) and abiotic factors (phenolic compounds). In order to clarify the proteomic differences of Fusarium moniliforme under the action of phloridzin, and to explore the potential mechanism of F. moniliforme as the pathogen of ARD, the role of Fusarium spp. in ARD was further clarified. Methods In this paper, the quantitative proteomics method iTRAQ analysis technology was used to analyze the proteomic differences of F. moniliforme before and after phloridzin treatment. The differentially expressed protein was validated by qRT-PCR analysis. Results A total of 4535 proteins were detected, and 293 proteins were found with more than 1.2 times (P< 0.05) differences. In-depth data analysis revealed that 59 proteins were found with more than 1.5 times (P< 0.05) differences, and most proteins were consistent with the result of qRT-PCR. Differentially expressed proteins were influenced a variety of cellular processes, particularly metabolic processes. Among these metabolic pathways, a total of 8 significantly enriched KEGG pathways were identified with at least 2 affiliated proteins with different abundance in conidia and mycelium. Functional pathway analysis indicated that up-regulated proteins were mainly distributed in amino sugar, nucleotide sugar metabolism, glycolysis/ gluconeogenesis and phagosome pathways. Conclusions This study is the first to perform quantitative proteomic investigation by iTRAQ labeling and LC-MS/MS to identify differentially expressed proteins in F. moniliforme under phloridzin conditions. The results confirmed that F. moniliforme presented a unique protein profile that indicated the adaptive mechanisms of this species to phloridzin environments. The results deepened our understanding of the proteome in F. moniliforme in response to phloridzin inducers and provide a basis for further exploration for improving the efficiency of the fungi as biocontrol agents to control ARD.


2017 ◽  
Vol 159 ◽  
pp. 77-91 ◽  
Author(s):  
Jasmine Naru ◽  
Ritu Aggarwal ◽  
Ashok Kumar Mohanty ◽  
Usha Singh ◽  
Deepak Bansal ◽  
...  

Blood ◽  
2016 ◽  
Vol 127 (19) ◽  
pp. 2275-2280 ◽  
Author(s):  
Brendan M. Weiss ◽  
Sandy W. Wong ◽  
Raymond L. Comenzo

Abstract Systemic immunoglobulin light chain (LC) amyloidosis (AL) is a potentially fatal disease caused by immunoglobulin LC produced by clonal plasma cells. These LC form both toxic oligomers and amyloid deposits disrupting vital organ function. Despite reduction of LC by chemotherapy, the restoration of organ function is highly variable and often incomplete. Organ damage remains the major source of mortality and morbidity in AL. This review focuses on the challenges posed by emerging therapies that may limit the toxicity of LC and improve organ function by accelerating the resorption of amyloid deposits.


1991 ◽  
Vol 67 (7) ◽  
pp. 645-646 ◽  
Author(s):  
James H. McCroskery ◽  
Robert E. Schell ◽  
Robert P. Sprafkin ◽  
Larry J. Lantinga ◽  
Robert A. Warner ◽  
...  

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
W Nammas ◽  
S Uotila ◽  
J Teuho ◽  
M Pietila ◽  
J Airaksinen ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) can detect arterial inflammation in individuals with atherosclerosis, but the associations among different vascular territories for 18F-FDG uptake are not known. Purpose We explored any possible correlation between arterial inflammation quantified by 18F-FDG PET in the aorta, carotid arteries, and coronary arteries in patients presenting with acute coronary syndrome (ACS), or chronic coronary artery disease (CAD). Methods Prospectively, we performed hybrid computed tomography angiography and 18F-FDG PET in 43 patients (26 ACS and 17 chronic CAD) at 6.6 ± 5.7 days following invasive coronary angiography. 18F-FDG PET was performed 90 minutes after injection of 302.2 ± 28.4 MBq 18F-FDG. Arterial 18F-FDG uptake was measured in the thoracic aorta, carotid arteries, and coronary arteries, and expressed as the target-to-background ratio (TBR; the ratio between arterial maximal standardized uptake value normalized to blood pool mean standardized uptake value) in the whole artery, and in the most diseased segment (MDS). Results Mean age was 64.9 ± 9.1 years, 90.7% males. The whole artery 18F-FDG uptake was higher in the aorta than in the carotid arteries (median TBR 2.23, interquartile range [0.36] vs. 1.88 [0.42], p &lt; 0.001); whereas uptake in the coronary arteries was lower than in the aorta or carotid arteries (1.13 [0.23], p &lt; 0.001 both). Similarly, 18F-FDG uptake in the aortic MDS was higher than in the carotid MDS (2.75 [0.62] vs. 2.25 [0.63], p &lt; 0.001); whereas 18F-FDG uptake in the coronary MDS was the lowest (1.40 [0.33], p &lt; 0.001 both). These findings were consistent in both ACS and chronic CAD patients. The whole artery 18F-FDG uptake of the aorta and carotid arteries correlated in patients with ACS (r = 0.58, p = 0.002), but not in patients with chronic CAD (r = 0.21, p = 0.3). There was no correlation between the whole artery 18F-FDG uptake in the coronary arteries and either the aorta or carotid arteries in the whole cohort (r=-0.16, p = 0.2, r = 0.01, p = 0.9, respectively), in patients with ACS (r = 0.06, p = 0.7, r=-0.01, p = 0.9, respectively), or in those with chronic CAD (r=-0.4, p = 0.1, r=-0.09, p = 0.7, respectively). Conclusions In patients with ACS or chronic CAD, large arteries had higher 18F-FDG uptake than the coronary arteries. The intensity of 18F-FDG uptake in the coronary arteries did not correlate with that in the carotid arteries or the aorta, indicating that disease activity differs between large arteries and coronary arteries.


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