Decreased M1 macrophage polarization in dabigatran-treated Ldlr-deficient mice: Implications for atherosclerosis and adipose tissue inflammation

Feldmann, Kathrin; Grandoch, Maria; Kohlmorgen, Christina; Valentin, Birte; Gerfer, Stephen; Nagy, Nadine; Hartwig, Sonja; Lehr, Stefan; Fender, Anke C.; Fischer, Jens W.

doi:10.1016/j.atherosclerosis.2019.06.897

Cited by 20 publications

(13 citation statements)

References 35 publications

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“…However, due to the influence of various objective reasons, such as breeding cycle, feasibility, and other factors, current animal models of AAA are primarily rodents, 5 such as rats and mice, which were treated mainly by chemical induction and/or gene knockout techniques, including subcutaneous infusion of the angiotensin II-induced apolipoprotein E knockout (ApoE –/– ) mice model, 6 and intra-aortic perfusion of elastin-induced 7 and abluminal application of calcium chloride (CaCl 2 )-induced 8,9 rodent models. They can also be divided into three types according to their processing mechanisms: (1) collagen elastase diseases that cause AAA: intra-aortic perfusion or abluminal application of elastase 10 with or without oral beta-amino acrylic nitrile (BAPN) 11,12 or systematic blocking of the activity of transforming growth factor-beta (TGF-β) 13,14 ; (2) atherosclerosis causing AAA (most common in humans): ApoE –/– or low-density lipoprotein receptor knockout (LDLr –/– ) mice 15 with or without angiotensin-II (Ang II) subcutaneous infusion; and (3) inflammatory AAA (least common): abluminal application of CaCl 2 .…”

Section: Inside-out Inflammation Theory and Hemodynamicsmentioning

confidence: 99%

“…Chen et al 84 analyzed the genome data of human AAA patients and found that the incidence of AAA in women was lower than that in men (about 1:4), and may be due to the higher estrogen level which promoted the M2 phenotype transformation of macrophages. Feldmann et al 15 reported that dabigatran inhibited the progression of atherosclerosis in LDLr –/– mice by reducing the proinflammatory cytokines and accumulation of M1 macrophages in the aortic wall and PVAT. It is also reported that rivaroxaban, an oral factor Xa inhibitor that has been proved to be able to attenuate both Ang II- and CaCl 2 -induced AAA progressions, 85 reduced MMP9 expression and exerted anti-inflammatory and anti-oxidative stress properties in incubated human AAA tissues.…”

Section: Intraluminal Thrombus and Distribution Of Macrophage Subtypes: View Of Immunologymentioning

confidence: 99%

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Mechanisms of abdominal aortic aneurysm progression: A review

Gao

Guo

2021

Vasc Med

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Abdominal aortic aneurysm (AAA) is a common disease associated with significant cardiovascular morbidity and mortality. Up to now, there is still controversy on the choice of treatment method of AAA. Even so, the mechanisms of AAA progression are poorly defined, making targeting new therapies problematic. Current evidence favors an interaction of the hemodynamic microenvironment with local and systemic immune responses. In this review, we aim to provide an update of mechanisms in AAA progression, involving hemodynamics, perivascular adipose tissue, adventitial fibroblasts, vasa vasorum remodeling, intraluminal thrombus, and distribution of macrophage subtypes.

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Section: Inside-out Inflammation Theory and Hemodynamicsmentioning

confidence: 99%

Section: Intraluminal Thrombus and Distribution Of Macrophage Subtypes: View Of Immunologymentioning

confidence: 99%

Mechanisms of abdominal aortic aneurysm progression: A review

Gao

Guo

2021

Vasc Med

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“…Inflammation in AS. Inflammation runs through the beginning, progression, and complications of atherosclerosis [62]. Atherosclerosis is a complex, multimechanical disease.…”

Section: Nlrp3 Inflammasome and Asmentioning

confidence: 99%

NLRP3 Inflammasome: A Potential Alternative Therapy Target for Atherosclerosis

Yang

Yin

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Atherosclerosis (AS) is a complex and chronic inflammatory disease that occurs in multiple systems of the human body. It is an important pathological basis for a variety of diseases and a serious threat to human health. So far, many theories have been formed to explain the pathogenesis of atherosclerosis, among which “inflammation theory” has gradually become a research focus. This theory presents that inflammatory response runs through the whole progress of AS, inflammatory cells play as the main executors of AS, and inflammatory mediators are the key molecules of AS. In the inflammatory process of atherosclerosis, the role of NLRP3 in the atherosclerosis has gradually got the attention of researchers. NLRP3 is a kind of signal-transductional pattern recognition receptors (PRRs). After recognizing and binding to the damage factors, NLRP3 inflammasome will be assembled to activate IL-1β and caspase-1 pathways, resulting in promoting the inflammation process of AS, reducing the stability of the plaques, and finally increasing the incidence of adverse cardiovascular events. Taken above, the article will review the potential benefits of drugs targeting the NLRP3 inflammasome in the therapy of AS.

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“…At least five of such studies document protection against progression of atherosclerosis, including improved plaque stability, while on dabigatran (Lee et al 2012;Kadoglou et al 2012;Borissoff et al 2013;Pingel et al 2014;Preusch et al 2015). One protective mechanism may involve the dabigatran-mediated attenuation of pro-inflammatory M1 macrophages in the vessel wall, observed in Lldr À/À mice (Feldmann et al 2019).…”

Section: Coagulation Proteasesmentioning

confidence: 99%

Antithrombotic Therapy: Prevention and Treatment of Atherosclerosis and Atherothrombosis

Olie

Meijden

Spronk

et al. 2020

Handbook of Experimental Pharmacology

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Atherosclerosis is a multifactorial vascular disease that develops in the course of a lifetime. Numerous risk factors for atherosclerosis have been identified, mostly inflicting pro-inflammatory effects. Vessel injury, such as occurring during erosion or rupture of atherosclerotic lesions triggers blood coagulation, in attempt to maintain hemostasis (protect against bleeding). However, thrombo-inflammatory mechanisms may drive blood coagulation such that thrombosis develops, the key process underlying myocardial infarction and ischemic stroke (not due to embolization from the heart). In the blood coagulation system, platelets and coagulation proteins are both essential elements. Hyperreactivity of blood coagulation aggravates atherosclerosis in preclinical models. Pharmacologic inhibition of blood coagulation, either with platelet inhibitors, or better documented with anticoagulants, or both, limits the risk of thrombosis and may potentially reverse atherosclerosis burden, although the latter evidence is still based on animal experimentation. Patients at risk of atherothrombotic complications should receive a single antiplatelet agent (acetylsalicylic acid, ASA, or clopidogrel); those who survived an atherothrombotic event will be prescribed temporary dual antiplatelet therapy (ASA plus a P2Y12 inhibitor) in case of myocardial infarction (6-12 months), or stroke (<6 weeks), followed by a single antiplatelet agent indefinitely. High risk for thrombosis patients (such as those with peripheral artery disease) benefit from a combination of an anticoagulant and ASA. The price of gained efficacy is always increased risk of (major) bleeding; while tailoring therapy to individual needs may limit the risks to some extent, new generations of agents that target less critical elements of hemostasis and coagulation mechanisms are needed to maintain efficacy while reducing bleeding risks.

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Decreased M1 macrophage polarization in dabigatran-treated Ldlr-deficient mice: Implications for atherosclerosis and adipose tissue inflammation

Cited by 20 publications

References 35 publications

Mechanisms of abdominal aortic aneurysm progression: A review

Mechanisms of abdominal aortic aneurysm progression: A review

NLRP3 Inflammasome: A Potential Alternative Therapy Target for Atherosclerosis

Antithrombotic Therapy: Prevention and Treatment of Atherosclerosis and Atherothrombosis

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