scholarly journals Mosaicism of Mitochondrial Genetic Variation in Atherosclerotic Lesions of the Human Aorta

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Margarita A. Sazonova ◽  
Vasily V. Sinyov ◽  
Valeria A. Barinova ◽  
Anastasia I. Ryzhkova ◽  
Andrey V. Zhelankin ◽  
...  
Keyword(s):  
Fatty Infiltration ◽  
Atherosclerotic Lesion ◽  
Morphological Characteristics ◽  
Original Method ◽  
Human Aorta ◽  
Fibrous Plaque ◽  
Tissue Sections ◽  
A1555g Mutation ◽  
Atherosclerotic Lesions ◽  
Antiatherosclerotic Effect

Objective.The aim of the present study was an analysis of heteroplasmy level in mitochondrial mutations 652delG, A1555G, C3256T, T3336C, 652insG, C5178A, G12315A, G13513A, G14459A, G14846A, and G15059A in normal and affected by atherosclerosis segments of morphologically mapped aortic walls.Methods.We investigated the 265 normal and atherosclerotic tissue sections of 5 human aortas. Intima of every aorta was divided according to morphological characteristics into segments with different types of atherosclerotic lesions: fibrous plaque, lipofibrous plaque, primary atherosclerotic lesion (fatty streak and fatty infiltration), and normal intima from human aorta. PCR-fragments were analyzed by a new original method developed in our laboratory on the basis of pyrosequence technology.Results.According to the obtained data, mutations G12315A and G14459A are significantly associated with total and primary atherosclerotic lesions of intimal segments and lipofibrous plaques (P≤0.01andP≤0.05, accordingly). Mutation C5178A is significantly associated with fibrous plaques and total atherosclerotic lesions(P≤0.01). A1555G mutation shows an antiatherosclerotic effect in primary lesion in lipofibrous plaques(P≤0.05). Meanwhile, G14846A mutation is antiatherogenic for lipofibrous plaques(P≤0.05).Conclusion.Therefore, mutations C5178A, G14459A, G12315A, A1555G, and G14846A were found to be associated with atherosclerotic lesions.

scholarly journals A new method to detect apoptosis in paraffin sections: in situ end-labeling of fragmented DNA.

1993 ◽  
Vol 41 (1) ◽  
pp. 7-12 ◽  
Author(s):  
J H Wijsman ◽  
R R Jonker ◽  
R Keijzer ◽  
C J van de Velde ◽  
C J Cornelisse ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Staining Method ◽  
Morphological Characteristics ◽  
Image Cytometry ◽  
Apoptotic Cells ◽  
Dna Breaks ◽  
Paraffin Sections ◽  
Tissue Sections

Apoptosis (programmed cell death) can be difficult to detect in routine histological sections. Since extensive DNA fragmentation is an important characteristic of this process, visualization of DNA breaks could greatly facilitate the identification of apoptotic cells. We describe a new staining method for formalin-fixed, paraffin-embedded tissue sections that involves an in situ end-labeling (ISEL) procedure. After protease treatment to permeate the tissue sections, biotinylated nucleotides are in situ incorporated into DNA breaks by polymerase and subsequently stained with DAB via peroxidase-conjugated avidin. Staining of cells with the morphological characteristics of apoptosis was demonstrated in tissues known to exhibit programmed cell death, i.e., prostate and uterus after castration, tumors, lymph node follicles, and embryos. Apoptotic cells could be discriminated morphologically from areas of labeled necrotic cells, in which DNA degradation also occurs. Because apoptosis is relatively easily recognized in H&E-stained sections of involuting prostates of castrated rats, we used this model system to validate the ISEL method for the quantification of apoptotic cells. A high correlation was found between the fractions of ISEL-labeled cells and the fractions of apoptotic cells that were morphologically determined in adjacent sections. We conclude that ISEL is a useful technique for quantification of apoptosis in paraffin sections, especially for those tissues in which morphological determination is difficult. Furthermore, this new staining method enables the use of automated image cytometry for evaluating apoptosis.

scholarly journals Nitric oxide function in atherosclerosis

1997 ◽  
Vol 6 (1) ◽  
pp. 3-21 ◽  
Author(s):  
K. E. Matthys ◽  
H. Bult
Keyword(s):  
Nitric Oxide ◽  
Leukocyte Adhesion ◽  
Atherosclerotic Lesion ◽  
Vascular Wall ◽  
Early Event ◽  
No Production ◽  
Oxygen Intermediates ◽  
Atherosclerotic Lesions ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Atherosclerosis is a chronic inflammatory process in the intima of conduit arteries, which disturbs the endothelium-dependent regulation of the vascular tone by the labile liposoluble radical nitric oxide (NO) formed by the constitutive endothelial nitric oxide synthase (eNOS). This defect predisposes to coronary vasospasm and cardiac ischaemia, with anginal pain as the typical clinical manifestation. It is now appreciated that endothelial dysfunction is an early event in atherogenesis and that it may also involve the microcirculation, in which atherosclerotic lesions do not develop. On the other hand, the inflammatory environment in atherosclerotic plaques may result in the expression of the inducible NO synthase (iNOS) isozyme. Whether the dysfunction in endothelial NO production is causal to, or the result of, atherosclerotic lesion formation is still highly debated. Most evidence supports the hypothesis that constitutive endothelial NO release protects against atherogenesis e.g. by preventing smooth muscle cell proliferation and leukocyte adhesion. Nitric oxide generated by the inducible isozyme may be beneficial by replacing the failing endothelial production but excessive release may damage the vascular wall cells, especially in combination with reactive oxygen intermediates.

Lipoprotein-elastin interactions in human aorta fibrous plaque lesions

1981 ◽  
Vol 38 (1-2) ◽  
pp. 137-147 ◽  
Author(s):  
S.R. Srinivasan ◽  
C. Yost ◽  
B. Radhakrishnamurthy ◽  
E.R. Dalferes ◽  
G.S. Berenson
Keyword(s):  
Human Aorta ◽  
Fibrous Plaque

scholarly journals Properties of Lysosomes in Atherosclerotic Lesions of Human Aorta

1980 ◽  
Vol 8 (2) ◽  
pp. 321-327
Author(s):  
Masahiro KUROSAKA ◽  
Kazushi HIROHATA ◽  
Masumi USUI ◽  
Kimiko MUTO ◽  
Tsuneo IMANAKA ◽  
...  
Keyword(s):  
Human Aorta ◽  
Atherosclerotic Lesions

Platelet P-selectin facilitates atherosclerotic lesion development

Blood ◽  
2003 ◽  
Vol 101 (7) ◽  
pp. 2661-2666 ◽  
Author(s):  
Peter C. Burger ◽  
Denisa D. Wagner
Keyword(s):  
Atherosclerotic Lesion ◽  
Soluble Form ◽  
Wild Type ◽  
Lesion Development ◽  
Atherosclerotic Lesions ◽  
Lesion Growth ◽  
Microparticle Formation ◽  
Apoe Deficient Mouse ◽  
Atherosclerotic Lesion Development

P-selectin is an adhesion molecule expressed on activated platelets and endothelium. It is known to play an important role in atherosclerosis. P-selectin also circulates in plasma in a soluble form (sP-selectin), which induces procoagulant microparticle formation. We investigated the role of platelet versus endothelial P-selectin in generating sP-selectin and in the formation of atherosclerotic lesions in the apolipoprotein E (apoE)–deficient mouse model. For this we transplanted apoE−/−P-selectin−/− and apoE−/−P-selectin+/+ lethally irradiated mice with bone marrow of either genotype. Seven months after transplantation, we determined from the chimeric animals that the majority of circulating sP-selectin was of endothelial origin. Thus, in atherosclerosis, the procoagulant sP-selectin reflects endothelial rather than platelet activation. We found that endothelial P-selectin was crucial for the promotion of atherosclerotic lesion growth because in its absence only relatively small lesions developed. However, platelet P-selectin also contributed to the lesion development because lesions in wild-type recipients receiving transplants with wild-type platelets were 30% larger than those receiving P-selectin-deficient platelets (P < .008) and were more frequently calcified (80% versus 44%). In comparison with P-selectin wild-type animals, absence of either endothelial or platelet P-selectin inhibited migration of smooth muscle cells into the lesion. Thus, in addition to endothelium, platelets and their P-selectin also actively promote advanced atherosclerotic lesion development.

Pharmacological inhibition of C-C chemokine receptor 4 aggravates atherosclerosis through prevention of regulatory T cell recruitment to the lesions

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Amin ◽  
N Sasaki ◽  
S Horibe ◽  
S Kawauchi ◽  
K Hirata ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Chemokine Receptor ◽  
Flow Cytometric Analysis ◽  
Atherosclerotic Lesion ◽  
Plaque Formation ◽  
Atherosclerotic Lesions ◽  
Sites Of Action ◽  
Chemokine Receptor 4 ◽  
Deficient Mice

Abstract Background Regulatory T cells (Tregs) are demonstrated to play a protective role in the development of atherosclerosis. However, their sites of action in atherosclerosis remain unclear. Although C-C chemokine receptor 4 (CCR4) has been shown to contribute to the accumulation of Tregs in inflamed tissues and prevention of experimental autoimmune diseases, the role of CCR4 in Treg migration to atherosclerotic lesions and suppression of plaque formation remains unknown. Methods and results We intraperitoneally injected 8-week-old apolipoprotein E–deficient mice fed a normal diet with vehicle (n=9) or a 4-μg dose of a CCR4 antagonist (n=10) 3 times weekly for 8 weeks and evaluated atherosclerotic lesions at 16 weeks old. Administration of the CCR4 antagonist significantly aggravated atherosclerotic plaque formation (aortic sinus plaque area: 2.91±0.87×104 μm2 versus 5.41±0.98×104 μm2 in control vehicle-treated and CCR4 antagonist-treated mice, respectively; P&lt;0.05), associated with increased accumulation of macrophages and CD4+T cells in the plaques. Flow cytometric analysis revealed a decrease in Foxp3+ Tregs in the para-aortic lymph nodes and thoracoabdominal aortas of CCR4 antagonist-treated mice, along with a tendency toward increase in CD44highCD62Lloweffector T cells in para-aortic lymph nodes, indicating CCR4-dependent migration of Tregs to atherosclerotic lesions and their possible atheroprotective role. We observed no changes in splenic Foxp3+ Tregs and effector T cells following CCR4 antagonist treatment. We also investigated the effect of CCR4 blockade on advanced atherosclerosis using LDL receptor–deficient mice fed a high-cholesterol diet. Although 8-week treatment with the CCR4 antagonist led to a decrease in Foxp3+ Tregs in the atherosclerotic lesions, atherosclerotic lesion formation was not significantly affected, suggesting that CCR4-dependent Treg accumulation in atherosclerotic lesions is not critical for prevention of advanced atherosclerosis. Conclusions Our findings indicate an important role for CCR4 in promotion of Treg recruitment into atherosclerotic lesions and subsequent prevention of early atherosclerosis and suggest CCR4 as a novel therapeutic target for atherosclerosis. Funding Acknowledgement Type of funding source: None

Immune-Inflammation in Atherosclerosis: A New Twist in an Old Tale

2020 ◽  
Vol 20 (4) ◽  
pp. 525-545 ◽  
Author(s):  
Atefe Ghamar Talepoor ◽  
Hamed Fouladseresht ◽  
Shahdad Khosropanah ◽  
Mehrnoosh Doroudchi
Keyword(s):  
T Cells ◽  
T Cell ◽  
Drug Targets ◽  
Inflammatory Diseases ◽  
Atherosclerotic Lesion ◽  
Preventative Measures ◽  
Atherosclerotic Lesions ◽  
Adaptive Immune Cells ◽  
One Step ◽  
Immune Inflammation

Background and Objective: Atherosclerosis, a chronic and progressive inflammatory disease, is triggered by the activation of endothelial cells followed by infiltration of innate and adaptive immune cells including monocytes and T cells in arterial walls. Major populations of T cells found in human atherosclerotic lesions are antigen-specific activated CD4+ effectors and/or memory T cells from Th1, Th17, Th2 and Treg subsets. In this review, we will discuss the significance of T cell orchestrated immune inflammation in the development and progression of atherosclerosis. Discussion: Pathogen/oxidative stress/lipid induced primary endothelial wound cannot develop to a full-blown atherosclerotic lesion in the absence of chronically induced inflammation. While the primary inflammatory response might be viewed as a lone innate response, the persistence of such a profound response over time must be (and is) associated with diverse local and systemic T cell responses. The interplay between T cells and innate cells contributes to a phenomenon called immuneinflammation and has an impact on the progression and outcome of the lesion. In recent years immuneinflammation, an old term, has had a comeback in connecting the puzzle pieces of chronic inflammatory diseases. Conclusion: Taking one-step back and looking from afar at the players of immune-inflammation may help us provide a broader perspective of these complicated interactions. This may lead to the identification of new drug targets and the development of new therapies as well as preventative measures.

Eva1a ameliorates atherosclerosis by promoting re-endothelialization of injured arteries via Rac1/Cdc42/Arpc1b

2020 ◽  
Author(s):  
Jingxuan Li ◽  
Yingyu Chen ◽  
Jianing Gao ◽  
Yue Chen ◽  
Changping Zhou ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Cell Counting ◽  
Human Aorta ◽  
Atherosclerotic Lesions ◽  
Rna Transfection ◽  
Promising Therapeutic Target ◽  
Carotid Artery Injuries ◽  
Underlying Mechanisms ◽  
Interfering Rna ◽  
Novel Protein

Abstract Aims Eva-1 homologue 1 (Eva1a) is a novel protein involved in the regulation of cardiac remodelling and plaque stability, but little is known about its role in re-endothelialization and the development of atherosclerosis (AS). Thus, in the present study, we aimed to elucidate the function of Eva1a in re-endothelialization and AS. Methods and results Wire injuries of carotid and femoral arteries were established in Eva1a−/− mice. Eva1a-deficient mice were crossed with apolipoprotein E−/− (ApoE−/−) mice to evaluate AS development and re-endothelialization of carotid artery injuries. Denudation of the carotid artery at 3, 5, and 7 days was significantly aggravated in Eva1a−/− mice. The neointima of the femoral artery at 14 and 28 days was consequently exacerbated in Eva1a−/− mice. The area of atherosclerotic lesions was increased in Eva1a−/−ApoE−/− mice. To explore the underlying mechanisms, we performed transwell, scratch migration, cell counting kit-8, and bromodeoxyuridine assays using cultured human aorta endothelial cells (HAECs), which demonstrated that EVA1A promoted HAEC migration and proliferation. Proteomics revealed that the level of actin-related protein 2/3 complex subunit 1B (Arpc1b) was decreased, while Eva1a expression was absent. Arpc1b was found to be a downstream molecule of EVA1A by small interfering RNA transfection assay. Activation of Rac1 and Cdc42 GTPases was also regulated by EVA1A. Conclusion This study provides insights into anti-atherogenesis effects of Eva1a by promoting endothelium repair. Thus, Eva1a is a promising therapeutic target for AS.

scholarly journals Effect of Consumption Heated Oils with or without Dietary Cholesterol on the Development of Atherosclerosis

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1527 ◽  
Author(s):  
Che Idris ◽  
Kalyana Sundram ◽  
Ahmad Razis
Keyword(s):  
Palm Olein ◽  
Corn Oil ◽  
Rabbit Model ◽  
Dietary Cholesterol ◽  
Atherosclerotic Lesion ◽  
Fibrous Plaque ◽  
Considerable Length ◽  
Radical Processes ◽  
Heated Oils ◽  
Effect Of Feeding

Heating oils and fats for a considerable length of time results in chemical reactions, leading to the aggravation of a free radical processes, which ultimately contributes to atherosclerosis. Our study focused on elucidating the effect of feeding heated oils with or without dietary cholesterol on the development of atherosclerosis in rabbits. We heated palm olein and corn oil at 180 °C for 18 h and 9 h per day, respectively, for two consecutive days. Next, 20 male rabbits were divided into four groups and fed the following diet for 12 weeks: (i) heated palm olein (HPO); (ii) HPO with cholesterol (HPOC); (iii) heated corn oil (HCO); and (iv) HCO with cholesterol (HCOC). Plasma total cholesterol (TC) was significantly lower in the HCO group compared to the HCOC group. Atherosclerotic lesion scores for both fatty plaques and fatty streaks were significantly higher in the HCO and HCOC groups as compared to the HPO and HPOC groups. Additionally, fibrous plaque scores were also higher in the HCO and HCOC groups as compared to the HPO and HPOC groups. These results suggest that heated palm oil confers protection against the onset of atherosclerosis compared to heated polyunsaturated oils in a rabbit model.

Quantitative analysis of the expression of caspase 3 and caspase 9 in different types of atherosclerotic lesions in the human aorta

2015 ◽  
Vol 99 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Igor A. Sobenin ◽  
Yuri V. Bobryshev ◽  
Gleb A. Korobov ◽  
Evgeny N. Borodachev ◽  
Anton Y. Postnov ◽  
...  
Keyword(s):  
Quantitative Analysis ◽  
Caspase 3 ◽  
Human Aorta ◽  
Caspase 9 ◽  
Atherosclerotic Lesions ◽  
Different Types
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