181 research outputs found
Targeting inflammation to reduce cardiovascular disease risk
This joint themed section of the British Journal of Pharmacology and the British Journal of Clinical Pharmacology stems from a joint British Pharmacological Society – Italian Society of Pharmacology symposium held at the 37th National Congress of the Italian Society of Pharmacology in Naples (Italy) from 27 to 30 October 2015
Editorial: tertiary lymphoid organs (TLOs): powerhouses of disease immunity
No abstract available
"Blow my mind(in)" - Mindin neutralization for the prevention of atherosclerosis?
The hallmark features of atherosclerosis include accumulation of low-density lipoprotein
(LDL) carrying cholesterol in the vessel wall, formation of lipid laden foam cells and the
creation of a pro-inflammatory microenvironment. To date, no effective treatments are
clinically available for increasing cholesterol efflux from vascular macrophages and inducing
reverse cholesterol transport. In a recent article in Clinical Science, Zhang and colleagues
identify the extracellular matrix protein mindin/spondin 2 as a positive regulator of
atherosclerosis. Genetic knockout of mindin in apolipoprotein-E (apoE)-/- mice attenuated
atherosclerosis, foam cell formation and inflammation within the vessel wall. Conversely,
selective overexpression of mindin in macrophages in apoE-/- mice was sufficient to promote
a greater severity of atherosclerosis. Interestingly, foam cell formation was closely
associated with expression of cholesterol transporters (ABCA1 and ACBG1) that facilitate
cholesterol efflux. Liver X receptor-β (LXR-β) is a key modulator of cholesterol transporter
expression and formed direct interactions with mindin. Furthermore, the protective effects of
mindin deficiency on foam cell formation were blocked by inhibition of LXR-β. This article
highlights a novel role for mindin in modulating foam cell formation and atherosclerosis
development in mice through direct regulation of LXR-β. Thus far, direct targeting of LXR-β
via pharmacological agonists has proven problematic due to the lack of subtype selective
inhibitors and associated adverse effects. Indirect targeting of LXR-β, therefore, via mindin
inhibition offers a new therapeutic strategy for increasing LXR-β induced cholesterol efflux,
reducing foam cell formation and preventing or treating atherosclerosis
Antigen-presenting cells and antigen presentation in tertiary lymphoid organs
Tertiary lymphoid organs (TLOs) form in territorialized niches of peripheral tissues characterized by the presence of antigens; however, little is known about mechanism(s) of antigen handling by ectopic lymphoid structures. In this mini review, we will discuss the role of antigen-presenting cells and mechanisms of antigen presentation in TLOs, summarizing what is currently known about this facet of the formation and function of these tissues as well as identifying questions yet to be addressed
When, where and how to target vascular inflammation in the post-CANTOS era?
No abstract available
Light sheet fluorescence microscopy for quantitative 3D imaging of vascular remodelling
No abstract available
Extracellular vesicle signalling in atherosclerosis
Atherosclerosis is a major cardiovascular disease and in 2016, the World Health Organisation (WHO) estimated 17.5 million global deaths, corresponding to 31% of all global deaths, were driven by inflammation and deposition of lipids into the arterial wall. This leads to the development of plaques which narrow the vessel lumen, particularly in the coronary and carotid arteries. Atherosclerotic plaques can become unstable and rupture, leading to myocardial infarction or stroke. Extracellular vesicles (EVs) are a heterogeneous population of vesicles secreted from cells with a wide range of biological functions. EVs participate in cell-cell communication and signalling via transport of cargo including enzymes, DNA, RNA and microRNA in both physiological and patholophysiological settings. EVs are present in atherosclerotic plaques and have been implicated in cellular signalling processes in atherosclerosis development, including immune responses, inflammation, cell proliferation and migration, cell death and vascular remodeling during progression of the disease. In this review, we summarise the current knowledge regarding EV signalling in atherosclerosis progression and the potential of utilising EV signatures as biomarkers of disease
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