Small Interfering Ribonucleic Acid as Lipid-Lowering Therapy: Inclisiran in Focus

Abstract

The PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) enzyme interferes with the metabolism of low-density lipoprotein (LDL) cholesterol. Inhibition of PCSK9 results in lower LDL cholesterol levels, which can be achieved by different molecular pathways. Monoclonal antibodies targeting circulating PCSK9 have shown strong and persistent effects on lowering the LDL cholesterol level, while reducing the risk of future cardiovascular events. However, this therapy requires once- or twice-monthly administration in the form of subcutaneous injection. This dosing regimen might impact the therapy adherence in cardiovascular patients who often require multiple drugs with different dosing intervals. Small interfering ribonucleic acid (siRNA) represents a promising therapy approach for patients with elevated LDL cholesterol level despite optimized background statin therapy. Inclisiran is a synthesized siRNA which inhibits PCSK9 synthesis in the liver and provides sustained and durable lowering of LDL cholesterol with twice-yearly application and a good tolerability profile. Herein, we present an overview of the current available data and critical review of the major clinical trials which assessed safety and efficacy of inclisiran in different groups of patients with elevated LDL cholesterol level.

Deciphering the therapeutic potential of trimetazidine in rheumatoid arthritis via targeting mi-RNA128a, TLR4 signaling pathway, and adenosine-induced FADD-microvesicular shedding: In vivo and in silico study

“…Considering the increasing prevalence of rheumatoid arthritis around the world and the lack of effective drugs that cause fewer side effects, the development of drugs with greater efficacy is of utmost importance. Trimetazidine (TMZ), a commonly used drug in the treatment of coronary artery disease, increases conventional antianginal therapies by modulating cardiac metabolism ( Rakočević et al, 2023 ). Its antioxidant characteristics mitigate inflammatory responses by inhibiting the production of cytokines such as TNF-α, NFKB, and IL-6 in macrophages ( Dézsi, 2016 ).…”