MS336 REDUCTION OF EXISTING ATHEROSCLEROTIC PLAQUES: LIPID-LOWERING AND ANTI-INFLAMMATORY STRATEGIES PROMOTE LESION REGRESSION IN APOE3LEIDEN TRANSGENIC MICE

2010 ◽  
Vol 11 (2) ◽  
pp. 177
Author(s):  
P.Y. Wielinga ◽  
R. Kleemann ◽  
J. de Vries-vd Weij ◽  
K. Toet ◽  
P.C.N. Rensen ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Lipid Lowering ◽  
Atherosclerotic Plaques ◽  
Anti Inflammatory ◽  
Lesion Regression

Abstract 49: Elevating Apolipoprotein A-I Levels Promotes Atherosclerosis Regression in Diabetic Mice by Inhibiting Proliferation of Bone Marrow Monocyte Precursors

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Tessa J Barrett ◽  
Emilie Distel ◽  
Yoscar Ogando ◽  
Yaritzy M Astudillo ◽  
Jianhua Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transgenic Mice ◽  
Plasma Cholesterol ◽  
Atherosclerotic Lesion ◽  
Lipid Lowering ◽  
Diabetic Mice ◽  
Blood Monocytes ◽  
Post Surgery ◽  
Lesion Regression

Diabetes is a primary risk factor for cardiovascular diseases (CVD) and in clinical imaging studies is shown to impair the resolution of CVD, a process termed regression. We have also reported this failure of lesion regression in mouse models of diabetes, despite effective lipid lowering. This, in part, can be attributed to diabetes-driven monocytosis promoting continued monocyte infiltration into plaques. In non-diabetic settings apolipoprotein (apo) A-I and high-density lipoprotein (HDL) suppress leukocytosis and promote lesion regression. As low apoA-I/HDL is a typical feature of diabetic dyslipidemia this study aimed to establish whether raising apoA-I/HDL levels in vivo is an effective approach to reduce diabetes-driven leukocytosis and promote lesion regression. Aortic arches from hyperlipidemic Ldlr -/- mice were transplanted into WT, diabetic WT, and diabetic human apoA-I-overexpressing transgenic mice (transgenic mice have a 3-fold increase in HDL-cholesterol), and lesion composition assessed 2 weeks post-surgery. Following aortic transplantation into WT mice (i.e. normal lipid levels) we found regression, as assessed by change in plaque macrophage (mΦ) content relative to baseline control mice was achieved (68% mΦ reduction, P<0.001). Regression was impaired when aortas were transplanted into diabetic WT recipients (50% mΦ reduction, P<0.01). However, raising apoA-I/HDL levels in the setting of diabetes restored regression in diabetic mice (62% mΦ reduction, P<0.001). In vivo monocyte/mΦ trafficking analyses revealed that elevating apoA-I/HDL levels in diabetes improves atherosclerosis regression by reducing monocyte entry by 60% (P<0.01), and promoting mΦ egress from lesions (30% increase). We also found that greater apoA-I/HDL reduced blood monocytes by decreasing the proliferation of monocyte progenitors in the bone marrow (15-20% reduction, P<0.05), explaining, in part, how apoA-I/HDL promotes regression. Raising apoA-I/HDL levels promotes atherosclerotic lesion regression in diabetic mice. This may serve as a therapeutic strategy for patients with diabetes, who unlike WT mice, have reduced HDL levels and remain at an elevated risk for CVD despite effective plasma cholesterol lowering.

Statins and Inflammation in Cardiovascular Disease

2018 ◽  
Vol 23 (46) ◽  
pp. 7027-7039 ◽  
Author(s):  
Georgia Vogiatzi ◽  
Evangelos Oikonomou ◽  
Gerasimos Siasos ◽  
Sotiris Tsalamandris ◽  
Alexandros Briasoulis ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Lipid Lowering ◽  
Hmg Coa Reductase ◽  
Ample Evidence ◽  
Reductase Inhibitors ◽  
Immune System Activation ◽  
Hmg Coa Reductase Inhibitors ◽  
Anti Inflammatory ◽  
Artery Disease ◽  
Coa Reductase

Background: Chronic inflammation and immune system activation underlie a variety of seemingly unrelated cardiac conditions including not only atherosclerosis and the subsequent coronary artery disease but also peripheral artery disease, hypertension with target organ damage and heart failure. The beneficial effects of HMG-CoA reductase inhibitors or statins are mainly attributed to their ability to inhibit hepatic cholesterol biosynthesis. Beyond their lipid lowering activity, ample evidence exists in support of their potent anti-inflammatory properties which initiate from the inhibition of GTPase isoprenylation, activating a cataract of secondary pathways and extend to the inhibition and blocking of immune cell activation and interaction. </P><P> Objective: To summarize the anti-inflammatory mechanisms of statins in clinical and experimental settings in cardiovascular disease. </P><P> Methods: A systematic search of PubMed and the Cochrane Database was conducted in order to identify the majority of trials, studies, current guidelines and novel articles related to the subject. </P><P> Results: In vitro, statins have immuno-modulatory and anti-inflammatory effects, and they can exert antiatherosclerotic effects independently of their hypolipidemic actions. In addition, positive results have emerged from mechanistic and experimental studies on the active role of HMG-CoA reductase inhibitors in HF. By extrapolating those data in clinical setting, we further understand how HMG-CoA reductase inhibitors can beneficially affect not only systolic but also diastolic HF. </P><P> Conclusion: In this review article, we present the basic pathophysiologic data supporting the anti-inflammatory actions of statins in clinical and experimental settings and we link these mechanisms with confirmatory clinical data on the potent non lipid lowering effects of HMG-CoA reductase inhibitors.

Effects of Gentiana lutea root on vascular diseases

2020 ◽  
Vol 18 ◽  
Author(s):  
Gordana Joksic ◽  
Djordje Radak ◽  
Emina Sudar-Milovanovic ◽  
Milan Obradovic ◽  
Jelena Radovanovic ◽  
...  
Keyword(s):  
Recent Literature ◽  
Vascular Diseases ◽  
Lipid Lowering ◽  
Primary Data ◽  
Electronic Database ◽  
Active Components ◽  
Gentiana Lutea ◽  
Search Terms ◽  
Anti Oxidant ◽  
Anti Inflammatory

Background: Gentiana lutea (GL), commonly known as yellow gentian, bitter root, and bitterwort, belongs to family Gentianaceae. GL belongs to genus Gentiana, which is a rich natural source of iridoids, secoiridoids, xantones, flavonoids, triterpenoids, and carbohydrates. Medicinal plants from Gentiana species have anti-oxidant, anti-inflammatory, anti-mitogenic, anti-proliferative, and lipid-lowering effects, as well as a cardioprotective, hypotensive, vasodilator and anti-platelet activities. Objective: We reviewed the recent literature related to the effects of Gentiana species, and their active components on vascular diseases. Methods: Data used for this review were obtained by searching the electronic database [PUBMED/MEDLINE 1973 - February 2020]. The primary data search terms of interest were: Gentiana lutea, Gentienacea family, phytochemistry, vascular diseases, treatment of vascular diseases, anti-oxidant, anti-inflammatory, anti-atherogenic. Conclusion: Gentiana species and their constituents affect many different factors related to vascular disease development and progression. Therefore, Gentiana-based therapeutics represent potentially useful drugs for the management of vascular diseases.

scholarly journals Efficient aortic lymphatic drainage is necessary for atherosclerosis regression induced by ezetimibe

2020 ◽  
Vol 6 (50) ◽  
pp. eabc2697
Author(s):  
Kim Pin Yeo ◽  
Hwee Ying Lim ◽  
Chung Hwee Thiam ◽  
Syaza Hazwany Azhar ◽  
Caris Tan ◽  
...  
Keyword(s):  
Lymphatic Vessels ◽  
Lymphatic Drainage ◽  
Lymphatic Transport ◽  
Atherosclerotic Plaques ◽  
Tissue Fluid ◽  
Atherosclerosis Progression ◽  
Lymphatic Vasculature ◽  
Lesion Regression ◽  
Transport Of Macromolecules

A functional lymphatic vasculature is essential for tissue fluid homeostasis, immunity, and lipid clearance. Although atherosclerosis has been linked to adventitial lymphangiogenesis, the functionality of aortic lymphatic vessels draining the diseased aorta has never been assessed and the role of lymphatic drainage in atherogenesis is not well understood. We develop a method to measure aortic lymphatic transport of macromolecules and show that it is impaired during atherosclerosis progression, whereas it is ameliorated during lesion regression induced by ezetimibe. Disruption of aortic lymph flow by lymphatic ligation promotes adventitial inflammation and development of atherosclerotic plaque in hypercholesterolemic mice and inhibits ezetimibe-induced atherosclerosis regression. Thus, progression of atherosclerotic plaques may result not only from increased entry of atherogenic factors into the arterial wall but also from reduced lymphatic clearance of these factors as a result of aortic lymph stasis. Our findings suggest that promoting lymphatic drainage might be effective for treating atherosclerosis.

scholarly journals Anti-inflammatory effects of Capparis ecuadorica extract in phthalic-anhydride-induced atopic dermatitis of IL-4/Luc/CNS-1 transgenic mice

2020 ◽  
Vol 58 (1) ◽  
pp. 1263-1276
Author(s):  
Bo Ram Song ◽  
Su Jin Lee ◽  
Ji Eun Kim ◽  
Hyeon Jun Choi ◽  
Su Ji Bae ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Transgenic Mice ◽  
Phthalic Anhydride ◽  
Anti Inflammatory

Class B Scavenger Receptors BI and BII Protect Against LPS-induced Acute Lung Injury in Mice by Mediating LPS Clearance

2021 ◽  
Author(s):  
Irina N. Baranova ◽  
Alexander V. Bocharov ◽  
Tatyana G. Vishnyakova ◽  
Zhigang Chen ◽  
Anna A. Birukova ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Transgenic Mice ◽  
Neutrophil Infiltration ◽  
Lavage Fluid ◽  
Protective Role ◽  
Lung Damage ◽  
Wild Type ◽  
Class B ◽  
Anti Inflammatory

Recent studies suggest an anti-inflammatory protective role for class B scavenger receptor BI (SR-BI) in endotoxin-induced inflammation and sepsis. Other data, including ours, provide evidence for an alternative role of SR-BI, facilitating bacterial and endotoxin uptake, and contributing to inflammation and bacterial infection. Enhanced endotoxin susceptibility of SR-BI deficient mice due to their anti-inflammatory glucocorticoid deficiency complicates understanding SR-BI’s role in endotoxemia/sepsis, calling for use of alternative models. In this study, using hSR-BI and hSR-BII transgenic mice, we found that SR-BI and to a lesser extent its splicing variant SR-BII, protects against LPS-induced lung damage. At 20 hours after intratracheal LPS instillation the extent of pulmonary inflammation and vascular leakage was significantly lower in hSR-BI and hSR-BII transgenic mice compared to wild type mice. Higher bronchoalveolar lavage fluid (BALF) inflammatory cell count and protein content as well as lung tissue neutrophil infiltration found in wild type mice was associated with markedly (2-3 times) increased pro-inflammatory cytokine production as compared to transgenic mice following LPS administration. Markedly lower endotoxin levels detected in BALF of transgenic vs. wild type mice along with the significantly increased BODIPY-LPS uptake observed in lungs of hSR-BI and hSR-BII mice 20 hours after the IT LPS injection suggest that hSR-BI and hSR-BII-mediated enhanced LPS clearance in the airways could represent the mechanism of their protective role against LPS-induced acute lung injury.

scholarly journals Raman spectroscopy provides chemical mappings of atherosclerotic plaques in APOE•3 leiden transgenic mice

1998 ◽  
Vol 31 ◽  
pp. 500-501 ◽  
Author(s):  
T.J. Römer ◽  
H.P. Buschman ◽  
G.J. Puppels ◽  
J.F. Brennan ◽  
A. van der Laarse ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Transgenic Mice ◽  
Atherosclerotic Plaques

scholarly journals Bergamot Polyphenols Boost Therapeutic Effects of the Diet on Non-Alcoholic Steatohepatitis (NASH) Induced by “Junk Food”: Evidence for Anti-Inflammatory Activity

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1604 ◽  
Author(s):  
Maddalena Parafati ◽  
Antonella Lascala ◽  
Daniele La Russa ◽  
Chiara Mignogna ◽  
Francesca Trimboli ◽  
...  
Keyword(s):  
Weight Loss ◽  
Dietary Intervention ◽  
Inflammatory Activity ◽  
Lipid Lowering ◽  
Therapeutic Effects ◽  
Junk Food ◽  
Alcoholic Fatty Liver ◽  
Inflammatory Parameters ◽  
Hepatic Fat ◽  
Anti Inflammatory

Wrong alimentary behaviors and so-called “junk food” are a driving force for the rising incidence of non-alcoholic fatty liver disease (NAFLD) among children and adults. The “junk food” toxicity can be studied in “cafeteria” (CAF) diet animal model. Young rats exposed to CAF diet become obese and rapidly develop NAFLD. We have previously showed that bergamot (Citrus bergamia Risso et Poiteau) flavonoids, in the form of bergamot polyphenol fraction (BPF), effectively prevent CAF diet-induced NAFLD in rats. Here, we addressed if BPF can accelerate therapeutic effects of weight loss induced by a normocaloric standard chow (SC) diet. 21 rats fed with CAF diet for 16 weeks to induce NAFLD with inflammatory features (NASH) were divided into three groups. Two groups were switched to SC diet supplemented or not with BPF (CAF/SC±BPF), while one group continued with CAF diet (CAF/CAF) for 10 weeks. BPF had no effect on SC diet-induced weight loss, but it accelerated hepatic lipid droplets clearance and reduced blood triglycerides. Accordingly, BPF improved insulin sensitivity, but had little effect on leptin levels. Interestingly, the inflammatory parameters were still elevated in CAF/SC livers compared to CAF/CAF group after 10 weeks of dietary intervention, despite over 90% hepatic fat reduction. In contrast, BPF supplementation decreased hepatic inflammation by reducing interleukin 6 (Il6) mRNA expression and increasing anti-inflammatory Il10, which correlated with fewer Kupffer cells and lower inflammatory foci score in CAF/SC+BPF livers compared to CAF/SC group. These data indicate that BPF mediates a specific anti-inflammatory activity in livers recovering from NASH, while it boosts lipid-lowering and anti-diabetic effects of the dietary intervention.

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