Emerging Anti-Atherosclerotic Therapies

Abstract

Cardiovascular disease (CAD) is the main cause of morbidity and deaths in the western world. The development of atherosclerosis underlying CAD development begins early in human life. There are numerous genetic and environmental risk factors accelerating its progression which then leads to the occurrence of acute events. Despite considerable progress in determining risk factors, there is still a lot of work ahead since identified determinants are responsible only for a part of overall CAD risk. Current therapies are insufficient to successfully reduce the risk of atherosclerosis development. Therefore, there is a need for effective preventive measures of clinical manifestations of atherosclerosis since the currently available drugs cannot prevent the occurrence of even 70% of clinical events. The shift of the target from lipid metabolism has opened the door to many new therapeutic targets. Currently, the majority of known targets for anti-atherosclerotic drugs focus also on inflammation (a common mediator of many risk factors), mechanisms of innate and adaptive immunity in atherosclerosis, molecule scavengers, etc. The therapeutic potential of cyclodextrins, protein kinase inhibitors, colchicine, inhibitors of p38 mitogen-activated protein kinase (MAPK), lipid dicarbonyl scavengers, a monoclonal antibody targeting interleukin-1β, and P-selectin inhibitors is still not fully confirmed and requires confirmation in large clinical trials. The preliminary results look promising.

Natural products of traditional Chinese medicine treat atherosclerosis by regulating inflammatory and oxidative stress pathways

“…Antiplatelet drugs and statins are currently the most prevalent drugs for the clinical treatment of ASCVD (Kishore et al, 2018). Anakinra and canakinumab both block interleukin (IL)-1β, and tocilizumab blocks IL-6 that are inflammatory factors involved in the occurrence and development of AS and synthetic antioxidants such as probucol reduced cholesterol levels (Chistiakov et al, 2018;Gluba-Brzózka et al, 2021). However, the high cost and side effects of long-term drugs presently on the market and synthetic drugs under development have clarified that suitable alternatives are urgently needed.…”

Self-Similar Functional Circuit Models of Arteries and Deterministic Fractal Operators: Theoretical Revelation for Biomimetic Materials

“…According to investigation by the World Health Organization, about one-third of all deaths worldwide are caused by cardiovascular disease. Atherosclerosis is one of the most common cardiovascular diseases and has been extensively studied by epidemiologists [ 4 , 5 ]. High-risk vascular plaque (or vulnerable atheromatous plaque) is the focused object for medical detection and treatment among atherosclerotic diseases [ 6 ].…”

Therapeutic Strategies and Chemoprevention of Atherosclerosis: What Do We Know and Where Do We Go?

“…It specifically binds to PCSK-9 mRNA, inhibits its translation and switches off PCSK-9 synthesis, resulting in a substantial and long-lasting decrease of serum LDLc levels. Analysis of data from three clinical trials showed that inclisiran decreased LDLc concentration by 51%, total cholesterol by 37%, ApoB by 41% and lowered the incidence of significant negative cardiovascular events by 24% [12]. The main therapeutic indications of inclisiran are primary hypercholesterolemia and mixed dyslipidemia in monotherapy or combined with statins or other lipid-lowering agents in patients who cannot achieve LDLc goals.…”

“…Phase 2 of the RESCUE trial reported that subcutaneous administration of ziltivekimab in patients with high cardiovascular risk significantly reduced biomarkers of systemic inflammation and thrombosis known to promote the atherothrombotic process (hsCRP, fibrinogen, serum amyloid A, secretory phospholipase A2 and LP(a)). Treatment was well-tolerated and had no influence on the total cholesterol to HDLc ratio [12,85].…”

“…Despite considerable progress in atherosclerosis research, current therapies are insufficient to effectively treat this disease. It is appreciated that the currently available medicines cannot prevent the occurrence of even 70% of clinical events [12]. There is a need for effective preventive strategies and better therapeutic options for atherosclerosis.…”