Abstract
Cardiovascular disease is the leading cause of death worldwide, and its prevalence is increasing due to the aging of societies. Atherosclerosis, a type of chronic inflammatory disease that occurs in arteries, is considered to be the main cause of cardiovascular diseases such as ischemic heart disease or stroke. In addition, the inflammatory response caused by atherosclerosis confers a significant effect on chronic inflammatory diseases such as psoriasis and rheumatic arthritis. Here, we review the mechanism of action of the main causes of atherosclerosis such as plasma LDL level and inflammation; furthermore, we review the recent findings on the preclinical and clinical effects of antibodies that reduce the LDL level and those that neutralize the cytokines involved in inflammation. The apolipoprotein B autoantibody and anti-PCSK9 antibody reduced the level of LDL and plaques in animal studies, but failed to significantly reduce carotid inflammation plaques in clinical trials. The monoclonal antibodies against PCSK9 (alirocumab, evolocumab), which are used as a treatment for hyperlipidemia, lowered cholesterol levels and the incidence of cardiovascular diseases. Antibodies that neutralize inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17, and IL-12/23) have shown promising but contradictory results and thus warrant further research.
Highlights
In pilot clinical trials determining the effectiveness of anti-tumor necrosis factor (TNF)-α monoclonal antibody on psoriatic arthritis, carotid atherosclerotic plaques were found in 15.8% of patients who received TNF-α blockers, in contrast to 40.4% of those who received traditional DMARD consisting of sulfasalazine, methotrexate, cyclosporine, and leflunomide [21]
In another clinical trial that examined the 5-year cardiovascular events in patients with psoriasis, which was associated with cardiovascular disease, anti-TNF-α antibody therapy was shown to significantly reduce the cardiovascular risk compared with other treatments [70]
This review summarized the mechanisms of action of antibody-based treatments targeting low-density lipoprotein (LDL) and cytokines, which are the major causes of cardiovascular disease and atherosclerosis, and their results in recent clinical trials
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Statin, which is used as a treatment for hyperlipidemia, functions by lowering the LDL levels; importantly, a meta-analysis of several randomized controlled studies on statin reported that statin reduced both the mortality from all causes and the incidence rates of atherosclerotic cardiovascular diseases [5] This suggests that lipid is a critical factor in atherosclerosis. OxLDLcell increases the expression adhesion molecules at the sion of adhesion molecules the endothelial surface, leading to theofrecruitment of monocytes endothelial cell surface, leading to the recruitment of monocytes and other immune cells,toand promote and other immune cells, and promote synergy with the aforementioned phenomena induce the synergy with the aforementioned phenomena to induce the formation of atherosclerotic plaques Another key keymechanism mechanismthat that drives development of atherosclerosis is iminflammation [14].
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