Beyond Lipoprotein Receptors: Learning from Receptor Knockouts Mouse Models about New Targets for Reduction of the Atherosclerotic Plaque.

Author(s): V. G. Trusca, E. V. Fuior, A. V. Gafencu.

Journal Name: Current Molecular Medicine

Volume 15 , Issue 10 , 2015

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Abstract:

Atherosclerosis and its complications represent the leading death cause worldwide, despite many therapeutic developments. Atherosclerosis is a complex, multistage disease whereby perturbed lipid metabolism leads to cholesterol accumulation into the vascular walls and plaque formation. Generation of apoE-/- and LDLR-/- atherosclerosis mouse models opened the avenue for investigating the mechanisms of action for specific molecules. We focus herein on the involvement of non-lipoprotein receptors in atherogenesis, as revealed by their total or site-specific ablation in the aforementioned murine models. The receptors reviewed span a broad range, from molecules related to lipid metabolism (adiponectin receptors) to molecules whose connection with atherogenesis is less obvious (cannabinoid receptors). We also outline cross-transplantation studies which allowed uncoupling the lipid modulating effects from the inflammatory ones. For certain receptors, since knockouts were unavailable, pharmacological data are presented instead. We emphasize the contribution of the receptors to the pathology, based on functional criteria, such as oxidative stress, immune response, inflammation, angiogenesis. Controversial aspects regarding the pro- or anti- atherogenic activity of some receptors are highlighted. We assume these discrepancies are due to the experimental setup, animal models used, tissue-specific action, various isoforms analyzed, divergent signaling or cross-talk between metabolic and immune pathways. Understanding the influences of cellular receptors in the progression of atherosclerosis allows their modulation towards an antiatherogenic phenotype. The experimental studies in animal models were in some cases successfully extrapolated to humans leading to atheroma reduction, and we expect this to occur even to a greater extent, based on the newest achievements.

Keywords: Atherosclerosis, membrane receptors, mouse models, atherosclerotic plaque, endothelial dysfunction, macrophages, vascular smooth muscle cells.

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Article Details

VOLUME: 15
ISSUE: 10
Year: 2015
Page: [905 - 931]
Pages: 27
DOI: 10.2174/1566524016666151123110310
Price: $58

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