Platelet Integrin αIIbβ3 Antagonist Attenuates Atherosclerotic Plaque Formation and Progression of Atherosclerosis in ApoE-deficient Mice on a High-fat Diet

2018 ◽  
Vol 32 ◽  
pp. 114-115
Author(s):  
Jie Zhu ◽  
Yumei Nie ◽  
Birong Zhou
Keyword(s):  
Atherosclerotic Plaque ◽  
High Fat Diet ◽  
Plaque Formation ◽  
High Fat ◽  
Integrin Αiibβ3 ◽  
Atherosclerotic Plaque Formation ◽  
Deficient Mice ◽  
Progression Of Atherosclerosis

scholarly journals Dapagliflozin decreases atherosclerotic plaque instability via regulating macrophage pyroptosis

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
L Xu ◽  
Y Dai ◽  
K Yao ◽  
H Yang ◽  
A Sun ◽  
...  
Keyword(s):  
Microarray Analysis ◽  
Atherosclerotic Plaque ◽  
High Fat Diet ◽  
Foam Cell ◽  
Atherosclerotic Lesion ◽  
Plaque Formation ◽  
Public Institution ◽  
Foam Cell Formation ◽  
Diabetic Patients ◽  
High Fat

Abstract Background Vulnerable plaques are characterized by infiltration of inflammatory cells, playing a key role in the progression of acute coronary events. It's important to clarify the inflammatory mechanism of unstable plaque formation. Several clinical trials have demonstrated that dapagliflozin could reduce major adverse cardiac events in whether diabetic or non-diabetic patients. However, the underlying cardioprotective mechanism of dapagliflozin remains unclear. This study was aimed to investigate the role of dapagliflozin in regulating macrophage pyroptosis and vulnerable plaque formation. Methods 20 ApoE−/− mice (control) were fed with high fat diet while another 20 ApoE−/− mice were challenged with high fat diet plus dapagliflozin for 12 weeks. The extent and instability of atherosclerotic plaque was determined by oil-red staining, HE staining, immunofluorescence staining and electron microscopy. Changes in subsets of immune cells were evaluated by flow cytometry. Plasma cytokines were assessed by ELISA. Microarray analysis was applied to detect gene expressions while Western blot and real-time PCR was used to assess gene expression levels. Results Morphology studies revealed that dapagliflozin could inhibit plaque formation and reduce instability in ApoE−/− mice. FACS data showed that dapagliflozin could decrease CD11b+Ly6Chigh M1 macrophages differentiation and inhibit foam cells formation in ApoE−/− mice. Microarray analysis and in vitro studies exhibited that dapagliflozin could induce the down regulation of NLRP3, caspase-1, IL-1β, IL-18 and MMP-7/10/12/14 to retard macrophage pyroptosis and foam cell formation. Conclusions We have characterized a novel role for dapagliflozin in modulating atherosclerotic lesion development and progression. We envision that this study may provide several potential therapeutic targets for treatment of acute coronary syndromes. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Shanghai Sailing Program

Coenzyme Q10 attenuates platelet integrin αIIbβ3 signaling and platelet hyper-reactivity in ApoE-deficient mice

2020 ◽  
Vol 11 (1) ◽  
pp. 139-152
Author(s):  
Fuli Ya ◽  
Xiaohong Ruby Xu ◽  
Zezhong Tian ◽  
Reid C. Gallant ◽  
Fenglin Song ◽  
...  
Keyword(s):  
Coenzyme Q10 ◽  
High Fat Diet ◽  
High Fat ◽  
Integrin Αiibβ3 ◽  
Coq10 Supplementation ◽  
Deficient Mice

CoQ10 supplementation in ApoE−/− mice attenuates high-fat diet-induced platelet hyper-reactivity via down-regulating platelet αIIbβ3 signaling, and thus protecting against atherothrombosis.

P715Deletion of fibroblast activation protein decreases experimental atherosclerotic plaque formation and vulnerability

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Stein ◽  
J Weber ◽  
S Nusser-Stein ◽  
J Pahla ◽  
H Zhang ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Cross Sections ◽  
Aortic Root ◽  
Fibroblast Activation Protein ◽  
Plaque Formation ◽  
Type I ◽  
Plaque Vulnerability ◽  
Fibroblast Activation ◽  
Atherosclerotic Plaque Formation ◽  
Deficient Mice

Abstract Background Fibroblast activation protein (FAP) is a serine protease that is upregulated in sites of tissue remodeling, including arthritis, tumors and atherosclerosis. We have reported that FAP degrades type I collagen in human thin-cap fibroatheromata; its expression is enhanced in advanced human plaques and induced by inflammation. However, the role of endogenous FAP in atherosclerosis remains unknown. Purpose To investigate the effects of constitutive Fap loss-of-function on atherosclerotic plaque formation and vulnerability. Methods and results Male 8-week-old Apoe−/− Fap+/+ and Apoe−/− Fap−/− mice were fed a high-cholesterol diet (1.25% chol) for 12 weeks. En face analyses of thoracoabdominal aortae using Oil Red O (ORO) revealed decreased plaques in Apoe−/− Fap−/− mice (5.7±0.5%; n=21) compared to Apoe−/− Fap+/+ mice (10.7±0.7%; n=24; p<0.0001). In parallel, ORO analyses of serial aortic root cross sections showed diminished plaques in Fap-deficient mice (18.4±3.4% vs 27.6±2.1%). As a surrogate of plaque vulnerability, fibrous cap thickness was increased in Apoe−/− Fap−/− mice (65±6 mm vs 35±3 mm; p<0.01), whereas necrotic core size, plaque macrophages (CD68) and T cells (CD3) accumulation, as well as VCAM1 expression did not differ. These changes were independent of plasma triglycerides, total and LDL-cholesterol levels. Plasma of Fap-deficient mice showed decreased FAP activity compared to Fap wildtype controls. Notably, second harmonics generation in cross sections of aortic root plaques showed that the deposition and density of fibrillar collagens was enhanced in Fap-deficient (25.5±4.4%) compared to control plaques (13.8±2.5%; p<0.05). Consistently, Fap deletion led to an accumulation of uncleaved pre-COL3A1, a proteolytic target of FAP. Conclusions Constitutive Fap deletion decreases experimental atherosclerosis and features of plaque vulnerability. Thus, inhibition of FAP expression or activity may be a promising therapeutic target in atherosclerosis. Acknowledgement/Funding Swiss National Science Foundation, Swiss Heart Foundation

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