Lipoprotein-associated Phospholipase A2: Current Trends in Invitro Diagnostics

2021 ◽  
Vol 12 (4) ◽  
pp. 1138-1142
Author(s):  
Riji Thomas ◽  
Ajaikumar Sukumaran ◽  
Thushara Thomas ◽  
Deepa K Vijayan ◽  
Jofy K Paul ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Vascular Inflammation ◽  
Plaque Formation ◽  
Individual Risk ◽  
Atherosclerotic Plaques ◽  
Heart Attacks ◽  
Current Trends ◽  
Atherosclerotic Plaque Formation ◽  
Unstable Plaques ◽  
The Individual

Lipoprotein-associated phospholipase A2 is an imminent reliable precise biomarker for vascular inflammation involved in the development of unstable plaques in cardiovascular diseases. The atherosclerotic plaque formation, inflammation and rupture of arterial vessels lead to heart attacks and strokes in most of the cases. The vessel-specific inflammatory enzyme, Lipoprotein-associated phospholipase A2 shoot ups in response to the rupture of arterial vessels having atherosclerotic plaques. The accurate measurement of Lipoprotein-associated phospholipase A2 envisages the individual risk of a patient and the treatment can be customized based on the result.

scholarly journals Neutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endothelium

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ingrid Gomez ◽  
Ben Ward ◽  
Celine Souilhol ◽  
Chiara Recarti ◽  
Mark Ariaans ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Vascular Inflammation ◽  
Plaque Formation ◽  
Atherosclerotic Plaques ◽  
High Fat ◽  
Inflammatory Gene Expression ◽  
Disturbed Flow ◽  
Atherosclerotic Plaque Formation

AbstractNeutrophils are implicated in the pathogenesis of atherosclerosis but are seldom detected in atherosclerotic plaques. We investigated whether neutrophil-derived microvesicles may influence arterial pathophysiology. Here we report that levels of circulating neutrophil microvesicles are enhanced by exposure to a high fat diet, a known risk factor for atherosclerosis. Neutrophil microvesicles accumulate at disease-prone regions of arteries exposed to disturbed flow patterns, and promote vascular inflammation and atherosclerosis in a murine model. Using cultured endothelial cells exposed to disturbed flow, we demonstrate that neutrophil microvesicles promote inflammatory gene expression by delivering miR-155, enhancing NF-κB activation. Similarly, neutrophil microvesicles increase miR-155 and enhance NF-κB at disease-prone sites of disturbed flow in vivo. Enhancement of atherosclerotic plaque formation and increase in macrophage content by neutrophil microvesicles is dependent on miR-155. We conclude that neutrophils contribute to vascular inflammation and atherogenesis through delivery of microvesicles carrying miR-155 to disease-prone regions.

Abstract 444: Semaphorin3A Reduces Atherosclerotic Plaque Formation in ApoE Knock Out Mice Through Regulation of M2 Type Macrophage Migration

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Talin Ebrahimian ◽  
Maryam Heidari ◽  
David Simon ◽  
Hojatollah Vali ◽  
Craig A Mandato ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Inflammatory Diseases ◽  
Plaque Formation ◽  
Atherosclerotic Plaques ◽  
M2 Macrophages ◽  
Aortic Sinus ◽  
Knock Out ◽  
Atherosclerotic Plaque Formation ◽  
Beta 1 Integrin

Objective: Recent data point to an important immunomodulatory role for neural guidance molecules, including semaphorin 3a (Sema-3A), in inflammatory diseases. Sema-3A is a secreted member of the Sema family and is produced by several immune cells including macrophages. We found that Sema-3A receptors are expressed in macrophages and in atherosclerotic plaques. Approach and results: To investigate the role of Sema-3A in atherosclerosis, ApoE-/- mice were administered with a Sema-3A overexpressing or a control plasmid and were fed a high fat diet for 9 weeks. Sema-3A receptors were expressed in macrophages and atherosclerotic plaques. Our results show that Sema-3A overexpressing mice had significantly smaller atherosclerotic plaques than control mice in the aortic sinus (0.3±0.02 vs. 0.4±0.03 mm 2 ), the brachiocephalic artery (0.04±0.01 vs. 0.1±0.01 mm 2 ) and the aorta (9.5±1.4 vs 15.3±2.9%), assessed by oil red O staining. No differences were observed in plaque stability, measured by collagen and smooth muscle cell alpha-actin staining. However, there was significantly less (2-fold) macrophage content in the plaques of Sema-3A compared to control mice, associated with decreased circulating monocytes determined by flow cytometry as cd11b positive and Gr-1 negative cells (4.97±0.74 vs. 7.2±0.62%). To better define the involved mechanisms, we investigated macrophage function In vitro and found that recombinant Sema-3A increased by 4 fold migration of M2 but not M1 macrophages. In addition, active beta-1 integrin expression was significantly enhanced (2-fold) by Sema-3A in human M2 macrophages. Importantly, Sema-3A induced a significant increase (by 50%) of focal adhesion kinase phosphorylation. Conclusions: Our data show that Sema-3A prevents atherosclerotic plaque formation in ApoE -/- mice. This may be due in part to enhanced motility and function of M2 macrophages through regulation of beta-1 integrin.

scholarly journals Targeting Platelet in Atherosclerosis Plaque Formation: Current Knowledge and Future Perspectives

2020 ◽  
Vol 21 (24) ◽  
pp. 9760
Author(s):  
Lei Wang ◽  
Chaojun Tang
Keyword(s):  
Risk Factors ◽  
Molecular Mechanisms ◽  
Vascular System ◽  
Current Knowledge ◽  
Vascular Inflammation ◽  
Plaque Formation ◽  
Inflammatory Factors ◽  
Future Perspectives ◽  
Atherosclerotic Plaque Formation

Besides their role in hemostasis and thrombosis, it has become increasingly clear that platelets are also involved in many other pathological processes of the vascular system, such as atherosclerotic plaque formation. Atherosclerosis is a chronic vascular inflammatory disease, which preferentially develops at sites under disturbed blood flow with low speeds and chaotic directions. Hyperglycemia, hyperlipidemia, and hypertension are all risk factors for atherosclerosis. When the vascular microenvironment changes, platelets can respond quickly to interact with endothelial cells and leukocytes, participating in atherosclerosis. This review discusses the important roles of platelets in the plaque formation under pro-atherogenic factors. Specifically, we discussed the platelet behaviors under disturbed flow, hyperglycemia, and hyperlipidemia conditions. We also summarized the molecular mechanisms involved in vascular inflammation during atherogenesis based on platelet receptors and secretion of inflammatory factors. Finally, we highlighted the studies of platelet migration in atherogenesis. In general, we elaborated an atherogenic role of platelets and the aspects that should be further studied in the future.

scholarly journals Melanocortin overexpression limits diet-induced inflammation and atherosclerosis in LDLR−/− mice

2018 ◽  
Vol 236 (3) ◽  
pp. 111-123 ◽  
Author(s):  
Salla Nuutinen ◽  
Liisa Ailanen ◽  
Eriika Savontaus ◽  
Petteri Rinne
Keyword(s):  
Atherosclerotic Plaque ◽  
Vascular Inflammation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Plaque Formation ◽  
Western Diet ◽  
Low Density ◽  
Long Term Effects ◽  
Melanocortin System ◽  
Atherosclerotic Plaque Formation

Atherosclerosis is a chronic inflammatory disease of the arteries. The disease is initiated by endothelial dysfunction that allows the transport of leukocytes and low-density lipoprotein into the vessel wall forming atherosclerotic plaques. The melanocortin system is an endogenous peptide system that regulates, for example, energy homeostasis and cardiovascular function. Melanocortin treatment with endogenous or synthetic melanocortin peptides reduces body weight, protects the endothelium and alleviates vascular inflammation, but the long-term effects of melanocortin system activation on atheroprogression remain largely unknown. In this study, we evaluated the effects of transgenic melanocortin overexpression in a mouse model of atherosclerosis. Low-density lipoprotein receptor-deficient mice overexpressing alpha- and gamma3-MSH (MSH-OE) and their wild-type littermates were fed either a regular chow or Western-style diet for 16 weeks. During this time, their metabolic parameters were monitored. The aortae were collected for functional analysis, and the plaques in the aortic root and arch were characterised by histological and immunohistochemical stainings. The aortic expression of inflammatory mediators was determined by quantitative PCR. We found that transgenic MSH-OE improved glucose tolerance and limited atherosclerotic plaque formation particularly in Western diet-fed mice. In terms of aortic vasoreactivity, MSH-OE blunted alpha1-adrenoceptor-mediated vasoconstriction and enhanced relaxation response to acetylcholine, indicating improved endothelial function. In addition, MSH-OE markedly attenuated Western diet-induced upregulation of proinflammatory cytokines (Ccl2, Ccl5 and Il6) that contribute to the pathogenesis of atherosclerosis. These results show that the activation of the melanocortin system improves glucose homeostasis and limits diet-induced vascular inflammation and atherosclerotic plaque formation.

scholarly journals Loss of soluble guanylyl cyclase in platelets contributes to atherosclerotic plaque formation and vascular inflammation

2021 ◽  
Author(s):  
Carina Mauersberger ◽  
Hendrik B Sager ◽  
Jana Wobst ◽  
Tan An Dang ◽  
Laura Lambrecht ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Guanylyl Cyclase ◽  
Leukocyte Adhesion ◽  
Vascular Inflammation ◽  
Soluble Guanylyl Cyclase ◽  
Plaque Formation ◽  
Allele Carrier ◽  
Atherosclerotic Plaque Formation ◽  
Angiopoietin 1

Aim: The role of platelets in atherosclerosis remains incompletely understood. Variants in genes encoding the soluble guanylyl cyclase (sGC) in platelets are associated with coronary artery disease (CAD) risk. Here we sought to investigate the contribution of platelet sGC to atherosclerosis and the therapeutic potential of targeting sGC in atherosclerosis. Methods and Results: We genetically deleted sGC in platelets of atherosclerosis-prone Ldlr-/- mice. By intravital fluorescence microscopy such Pf4-Cre+Gucy1b1flox/floxLdlr-/- mice displayed enhanced leukocyte adhesion to atherosclerotic plaques in comparison with their litter mates. Moreover, histological and flow cytometry analyses revealed more numerous inflammatory leukocytes and larger plaque sizes in aortic tissue of Ldlr-/- mice lacking sGC in platelets. In vitro, supernatant from activated platelets lacking sGC promoted leukocyte adhesion to endothelial cells (EC) via enhanced EC activation. Using cytokine profiling, we identified reduced angiopoietin-1 release by Pf4-Cre+Gucy1b1flox/flox and human GUCY1A1 risk allele carrier platelets to be responsible for enhanced activation of EC and subsequent leukocyte adhesion. Pharmacological sGC stimulation increased platelet angiopoietin-1 release in vitro and reduced recruitment of adoptively transferred leukocytes in Ldlr-/- mice fed a Western diet. Pharmacological sGC stimulation further reduced atherosclerotic plaque formation and vascular inflammation. Conclusion: Loss of sGC in platelets contributes to atherosclerotic plaque formation via reduced release of the soluble factor angiopoietin-1 and, subsequently, enhanced leukocyte recruitment. Pharmacological sGC stimulation might represent a novel therapeutic strategy to prevent and treat CAD.

scholarly journals ADAMTS13 reduces vascular inflammation and the development of early atherosclerosis in mice

Blood ◽  
2012 ◽  
Vol 119 (10) ◽  
pp. 2385-2391 ◽  
Author(s):  
Chintan Gandhi ◽  
Mohammad Moshahid Khan ◽  
Steven R. Lentz ◽  
Anil K. Chauhan
Keyword(s):  
Atherosclerotic Plaque ◽  
Leukocyte Adhesion ◽  
Vascular Inflammation ◽  
Fold Increase ◽  
Plaque Formation ◽  
Aortic Sinus ◽  
Atherosclerotic Lesions ◽  
Atherosclerotic Plaque Formation ◽  
Von Willebrand ◽  
Early Atherosclerosis

Abstract ADAMTS13, a metalloprotease, plays a pivotal role in preventing spontaneous microvascular thrombosis by cleaving hyperactive ultra large von Willebrand factor multimers into smaller, less active multimers. Reduced ADAMTS13 activity in plasma has been described in many diseases associated with systemic inflammation. It remains uncertain, however, whether ADAMTS13 contributes to disease pathogenesis or rather simply serves as an inflammation-associated marker. We hypothesized that, by decreasing vascular inflammation, ADAMTS13 reduces the development of early atherosclerotic plaques. Using intravital fluorescence microscopy, we observed excessive leukocyte adhesion and accelerated atherosclerotic plaque formation at the carotid sinus of Adamts13−/−/ApoE−/− mice compared with ApoE−/− mice fed a high-fat Western diet. At 4 months of age, there was a significant increase in atherosclerosis in the aorta and aortic sinus of Adamts13−/−/ApoE−/− mice compared with ApoE−/− mice. Interestingly, we detected a 2-fold increase in macrophage recruitment to the atherosclerotic plaque of the Adamts13−/−/ApoE−/− mice compared with ApoE−/− mice, suggesting that the atherosclerotic lesions in these mice were not only larger but also more inflammatory. These findings reveal a new functional role for the antithrombotic enzyme ADAMTS13 in reducing excessive vascular inflammation and plaque formation during early atherosclerosis.

A Cytochemical Study of Glucose-6-Phosphatase (G-6-PASE) in Cells Participating in Atherogenesis of Rabbit Aorta

1975 ◽  
Vol 33 ◽  
pp. 460-461
Author(s):  
Sidney D. Kobernick ◽  
Edna A. Elfont ◽  
Neddra L. Brooks
Keyword(s):  
Lipid Metabolism ◽  
New Zealand ◽  
Aortic Wall ◽  
Rabbit Aorta ◽  
Plaque Formation ◽  
Metabolic Changes ◽  
Atherosclerotic Plaques ◽  
Cytochemical Study ◽  
Cellular Alteration ◽  
New Zealand White Rabbits

This cytochemical study was designed to investigate early metabolic changes in the aortic wall that might lead to or accompany development of atherosclerotic plaques in rabbits. The hypothesis that the primary cellular alteration leading to plaque formation might be due to changes in either carbohydrate or lipid metabolism led to histochemical studies that showed elevation of G-6-Pase in atherosclerotic plaques of rabbit aorta. This observation initiated the present investigation to determine how early in plaque formation and in which cells this change could be observed.Male New Zealand white rabbits of approximately 2000 kg consumed normal diets or diets containing 0.25 or 1.0 gm of cholesterol per day for 10, 50 and 90 days. Aortas were injected jin situ with glutaraldehyde fixative and dissected out. The plaques were identified, isolated, minced and fixed for not more than 10 minutes. Incubation and postfixation proceeded as described by Leskes and co-workers.

The importance and significance of gene polymorphisms in preeclampsia

2016 ◽  
pp. 45-49
Author(s):  
P.N. Veropotvelyan ◽  
◽  
I.S. Tsehmistrenko ◽  
N.P. Veropotvelyan ◽  
N.S. Rusak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Systematic Review ◽  
Early Diagnosis ◽  
Gene Polymorphisms ◽  
Individual Risk ◽  
Extended Study ◽  
Stress Genes ◽  
Detoxification System ◽  
The Individual ◽  
The Relationship

Was to conduct a systematic review of data on the relationship between polymorphisms genes of detoxification system and development of preeclampsia (РЕ). Рresents the main genes of detoxification system (GSTPI, GSTМI, GSTТI, GРХI, ЕРНХI, SOD-2, SOD-3, CYPIAL, MTHЕR, MTR) and their functions. Of interest is the possibility of calculating the individual risk of PE based on the results about the presence of a combination of different polymorphisms in the genotype of the female. Question about early diagnosis of РЕ remains controversial and not fully understood. It is necessary to conduct further in-depth, extended study of this problem. Key words: preeclampsia, oxidative stress, genes of the detoxification system.

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