Targeting Foam Cell Formation in Atherosclerosis: Therapeutic Potential of Natural Products

Ca2+ Flux: Searching for a Role in Efferocytosis of Apoptotic Cells in Atherosclerosis

“…This conclusion stems from the knowledge that, without being ingested by neighboring vital macrophages, old macrophage foam cells die, they trigger an inflammatory response, and their bodies build up to form an ever-growing necrotic lipid core, which ultimately renders the plaque susceptible to rupture and cause even fatal atherothrombotic complications. Therefore, understanding cellular Ca 2+ metabolism and the related molecules/pathways which are involved in the generation of foam cells and in decreased efferocytic engulfment of ACs are of great importance when considering to attenuate the progression of atherosclerotic lesions [18]. In this regard, Ca 2+ plays a physiological and anti-atherosclerotic role by promoting the migration and survival of macrophages, and by enhancing the secretion of anti-inflammatory cytokines by them.…”

“…Statins are a class of drugs which inhibit the activity of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, the rate-controlling enzyme in the pathway of cholesterol biosynthesis [176]. They increase the activity of hepatic low-density lipoprotein receptors and thereby hepatic uptake of circulating LDL-particles, which lower the concentration of plasma LDL-cholesterol [177] and successfully decrease CVD, MI, and ischemic stroke [18,178,179]. Statins are divided in two main groups, hydrophilic statins such as fluvastatin, rosuvastatin, and pravastatin and lipophilic statins such as atorvastatin as well as simvastatin [18].…”

“…They increase the activity of hepatic low-density lipoprotein receptors and thereby hepatic uptake of circulating LDL-particles, which lower the concentration of plasma LDL-cholesterol [177] and successfully decrease CVD, MI, and ischemic stroke [18,178,179]. Statins are divided in two main groups, hydrophilic statins such as fluvastatin, rosuvastatin, and pravastatin and lipophilic statins such as atorvastatin as well as simvastatin [18]. Interestingly, of the statins, both hydrophilic statins (fluvastatin and pravastatin) and a lipophilic statin (atorvastatin) have been found to inhibit inorganic phosphate-induced apoptosis and the related calcification of culture VSMCs via the Gas6-mediated survival pathway [180,181].…”

“…A large and ever-growing body of literature has demonstrated that the most important steps in the formation of atherosclerotic plaques are the accumulation of inflammatory cells (viz. macrophages and dendritic cells), foam cell formation, and defective efferocytic removal of ACs in the plaques [17,18]. Most importantly, defective efferocytosis of inflammatory apoptotic macrophages and macrophage foam cells results in their secondary necrosis and thereby contributes to the formation of an enlarged necrotic core, which weakens the plaque and makes it susceptible to rupture [19].…”

<p>Isoborneol Attenuates Low-Density Lipoprotein Accumulation and Foam Cell Formation in Macrophages</p>

“…2 Mono-nuclear cells migrate to the sub-endothelial to be activated and differentiated into macrophages, and macrophages can phagocytose modified low-density lipoprotein to form early foam cells when the scavenger receptor is activated. 3,4 Foam cells will rupture and die with this constant accumulation of lipids. 5 Foam cells, therefore, serve not only as marker cells for the early stage of arteriosclerosis 6 but also participate in the entire atherosclerotic lesion process.…”