Title:Beyond Lipoprotein Receptors: Learning from Receptor Knockouts Mouse Models about New Targets for Reduction of the Atherosclerotic Plaque.
Volume: 15
Issue: 10
Author(s): V. G. Trusca, E. V. Fuior and A. V. Gafencu
Affiliation:
Keywords:
Atherosclerosis, membrane receptors, mouse models, atherosclerotic plaque, endothelial dysfunction,
macrophages, vascular smooth muscle cells.
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.
