Atherosclerosis: Molecular Pathogenesis and Therapeutic Interventions

Abstract

Atherosclerosis is a multifactor condition and driving force behind many cardiovascular diseases. Moreover, it remains a leading cause of mortality worldwide. The current therapies, including statins and fibrates, focus mainly on lipid lowering. However, this condition is characterized by various biological pathways, particularly the oxidized LDL uptake by macrophages, chronic inflammation, or vascular smooth muscle cells proliferation, migration, and phenotypic switching, which forces the researchers to explore the numerous molecular pathways standing behind those processes. Despite a lot research on this topic was conducted, the need of finding new therapeutic methods based on the molecular pathogenesis still remains. In this review, we summarize the involvement of the lead signaling pathways in atherosclerosis: transforming growth factor beta (TGF-β), mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), as well as the functions of cell cycle proteins in its pathogenesis. We are going to put an emphasis on the cyclin-dependent kinases (CDKs) 5 and 9, as the driving forces behind the pathological conditions. Furthermore, we describe the novel therapeutic interventions, including noncoding RNA strategies and proteolysis targeting chimeras (PROTACs), as they are important candidates for future therapies. Our insights may help in the thorough understanding of the atherosclerosis pathogenesis and finding the future therapeutic interventions.

Keywords

atherosclerosis / CDK5 / CDK9 / miRNA / PROTACs / siRNA

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