Schematic representation of non-lipoprotein receptors, as promising targets for atherosclerosis plaque regression. The figure illustrates the main targeted receptors expressed on the key cells of the atheromatous plaque: endothelial cells (EC), macrophages (MΦ), dendritic cells (DC), smooth muscle cells (SMC) and activated platelets (PLT). In order to simplify the picture, the mainly atheroprotective (green) and predominantly atherogenic receptors (red) are presented on two different macrophages or grouped on SMC and on the endothelium layer.
Atherosclerosis and its complications represent the leading death cause worldwide, despite many therapeutic developments. Atherosclerosis is a complex, multi-stage disease whereby perturbed lipid metabolism leads to cholesterol accumulation into the vascular walls and plaque formation. Generation of apoE-/- and LDLR-/- atherosclerosis mouse models...
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... (i) pharmacological modulation by the use of agonists or antagonists in an atherosclerosis mouse model; (ii) generation of double knockout mice by ablation of a specific gene on the background of an atherosclerosis model; if the complete ablation has lethal effect, partial deletion or conditional expression can be obtained and analyzed. In Fig. (1), we depicted these receptors on the most important cell types found in the atheroma plaque according to their main pro-or anti-atherogenic action (showed in red, respectively green color, in the figure). Important findings regarding the therapeutic potential of receptors involved in the various events aforementioned are discussed ...
... of new therapeutic approaches for atherosclerosis. Thus, we discussed herein the main non-lipoprotein receptors, not related to the lipid metabolism, used as targets for atheroma regression, as overviewed in Table 1. Their cellular distribution and their positive or negative effects in the atheromatous plaque are schematically illustrated in Fig. (1). Atherosclerosis is a tremendously complex process regarding the simultaneous dysregulation of multiple pathways in various cell types. We have only focused on the main receptors described in the literature as potential targets, based on murine knockout studies. Despite the accumulation of remarkable data which enhanced our general ...
Background: Apolipoprotein E (apoE) is an anti-atherosclerotic protein associated with almost all plasma lipoproteins. Fullerenol (Full-OH) contains the fullerene hydrophobic cage and several hydroxyl groups that could be derivatized to covalently bind various molecules. Herein, we aimed to produce fullerenol-based nanoparticles carrying apoE3 (Full-apoE) and test their anti-atherosclerotic effects. Methods: Full-apoE nanoparticles were obtained from Full-OH activated to reactive cyanide ester fullerenol derivative that was further reacted with apoE protein. To test their effect, the nanoparticles were administered to apoE-deficient mice for 24 h or 3 weeks. ApoE part of the nanoparticles was determined by Western Blot and quantified by ELISA. Atherosclerotic plaque size was evaluated after Oil Red O staining and the gene expression was determined by Real-Time PCR. Results: Full-apoE nanoparticles were detected mainly in the liver, and to a lesser extent in the kidney, lung, and brain. In the plasma of the Full-apoE-treated mice, apoE was found associated with very-low-density lipoproteins and high-density lipoproteins. Treatment for 3 weeks with Full-apoE nanoparticles decreased plasma cholesterol levels, increased the expression of apolipoprotein A-I, ABCA1 transporter, scavenger receptor-B1, and sortilin, and reduced the evolution of the atheromatous plaques in the atherosclerotic mice. Conclusions: In experimental atherosclerosis, the administration of Full-apoE nanoparticles limits the evolution of the atheromatous plaques by decreasing the plasma cholesterol level and increasing the expression of major proteins involved in lipid metabolism. Thus, they represent a novel promising strategy for atherosclerosis therapy.
Cannabinoids are known to modulate cardiovascular functions including heart rate, vascular tone, and blood pressure in humans and animal models. Essential components of the endocannabinoid system, namely, the production, degradation, and signaling pathways of endocannabinoids have been described not only in the central and peripheral nervous system but also in myocardium, vasculature, platelets, and immune cells. The mechanisms of cardiovascular responses to endocannabinoids are often complex and may involve cannabinoid CB1 and CB2 receptors or non-CB1/2 receptor targets. Preclinical and some clinical studies have suggested that targeting the endocannabinoid system can improve cardiovascular functions in a number of pathophysiological conditions, including hypertension, metabolic syndrome, sepsis, and atherosclerosis. In this chapter, we summarize the local and systemic cardiovascular effects of cannabinoids and highlight our current knowledge regarding the therapeutic potential of endocannabinoid signaling and modulation.