Unsolved Issues of Atherosclerosis Prevention and of Adequate Lipid-lowering Therapy in Patients with Acute Ischemic Cerebrovascular Accident

The existing system of medical care for patients with acute cerebrovascular accident of atherothrombotic genesis, namely lipid metabolism disorders, the modern evidence base for lipid-lowering therapy in this category of patients and the feasibility of interdisciplinary interaction of cardiologists and neurologists were discussed at a meeting of the expert council of cardiologists and neurologists in Moscow on 2021 July 7.

Comparison of Selenium Nanoparticles and Sodium Selenite on the Alleviation of Early Atherosclerosis by Inhibiting Endothelial Dysfunction and Inflammation in Apolipoprotein E-Deficient Mice

Atherosclerosis and related cardiovascular diseases represent the greatest threats to human health, worldwide. Previous animal studies showed that selenium nanoparticles (SeNPs) and Na2SeO3 might have anti-atherosclerotic activity, but the underlying mechanisms are poorly elucidated. This study compared the anti-atherosclerotic activity of SeNPs stabilized with chitosan (CS-SeNPs) and Na2SeO3 and the related mechanism in a high-fat-diet-fed apolipoprotein E-deficient mouse model of atherosclerosis. The results showed that oral administration of both CS-SeNPs and Na2SeO3 (40 μg Se/kg/day) for 10 weeks significantly reduced atherosclerotic lesions in mouse aortae. Mechanistically, CS-SeNPs and Na2SeO3 not only alleviated vascular endothelial dysfunction, as evidenced by the increase of serum nitric oxide level and the decrease of aortic adhesion molecule expression, but also vascular inflammation, as evidenced by the decrease of macrophage recruitment as well as the expression of proinflammatory molecules. Importantly, these results were replicated within in-vivo experiments on the cultured human endothelial cell line EA.hy926. Overall, CS-SeNPs had a comparable effect with Na2SeO3 but might have more potential in atherosclerosis prevention due to its lower toxicity. Together, these results provide more insights into the mechanisms of selenium against atherosclerosis and further highlight the potential of selenium supplementation as a therapeutic strategy for atherosclerosis.

Curcumin as a Natural Remedy for Atherosclerosis: A Pharmacological Review

Curcumin, a natural polyphenolic compound present in Curcuma longa L. rhizomes, shows potent antioxidant, anti-inflammatory, anti-cancer, and anti-atherosclerotic properties. Atherosclerosis is a comprehensive term for a series of degenerative and hyperplasic lesions such as thickening or sclerosis in large- and medium-sized arteries, causing decreased vascular-wall elasticity and lumen diameter. Atherosclerotic cerebro-cardiovascular disease has become a major concern for human health in recent years due to its clinical sequalae of strokes and heart attacks. Curcumin concoction treatment modulates several important signaling pathways related to cellular migration, proliferation, cholesterol homeostasis, inflammation, and gene transcription, among other relevant actions. Here, we provide an overview of curcumin in atherosclerosis prevention and disclose the underlying mechanisms of action of its anti-atherosclerotic effects.

LDL-Cholesterol and Platelets: Insights into Their Interactions in Atherosclerosis

Atherosclerosis and its complications, including acute coronary syndromes, are the major cause of death worldwide. The two most important pathophysiological mechanisms underlying atherosclerosis include increased platelet activation and increased low-density lipoproteins (LDL) concentration. In contrast to LDL, oxidized (ox)-LDL have direct pro-thrombotic properties by functional interactions with platelets, leading to platelet activation and favoring thrombus formation. In this review, we summarize the currently available evidence on the interactions between LDL-cholesterol and platelets, which are based on (i) the presence of ox-LDL-binding sites on platelets, (ii) generation of ox-LDL by platelets and (iii) the role of activated platelets and ox-LDL in atherosclerosis. In addition, we elaborate on the clinical implications of these interactions, including development of the new therapeutic possibilities. The ability to understand and modulate mechanisms governing interactions between LDL-cholesterol and platelets may offer new treatment strategies for atherosclerosis prevention.

Smooth Muscle Cell-Proteoglycan-Lipoprotein Interactions as Drivers of Atherosclerosis

In humans, smooth muscle cells (SMCs) are the main cell type in the artery medial layer, in pre-atherosclerotic diffuse thickening of the intima, and in all stages of atherosclerotic lesion development. SMCs secrete the proteoglycans responsible for the initial binding and retention of atherogenic lipoproteins in the artery intima, with this retention driving foam cell formation and subsequent stages of atherosclerosis. In this chapter we review current knowledge of the extracellular matrix generated by SMCs in medial and intimal arterial layers, their relationship to atherosclerotic lesion development and stabilization, how these findings correlate with mouse models of atherosclerosis, and potential therapies aimed at targeting the SMC matrix-lipoprotein interaction for atherosclerosis prevention.

Dysfunctional HDL as a Therapeutic Target for Atherosclerosis Prevention

Hypercholesterolemia is one of the main risk factors for the development of atherosclerosis. Among the various lipoprotein classes, however, high density lipoproteins (HDL) are inversely associated with the incidence of atherosclerosis, since they are able to exert a series of atheroprotective functions. The central role of HDL within the reverse cholesterol transport, their antioxidant and anti-inflammatory properties and their ability to preserve endothelial homeostasis are likely responsible for HDL-mediated atheroprotection. However, drugs that effectively raise HDL-C failed to result in a decreased incidence of cardiovascular event, suggesting that plasma levels of HDL-C and HDL function are not always related. Several evidences are showing that different pathologic conditions, especially those associated with an inflammatory response, can cause dramatic alterations of HDL protein and lipid cargo resulting in HDL dysfunction. Established and investigational drugs designed to affect lipid metabolism and to increase HDL-C are only partly effective in correcting HDL dysfunction.