Pcsk9 Pathway-Noncoding Rnas Crosstalk: Emerging Opportunities for Novel Therapeutic Approaches in Inflammatory Atherosclerosis Publisher Pubmed



Raheem Lateef Alawsi G¹ ; Hadi Lafta M² ; Hashim Kzar H³ ; Samieva G⁴ ; Alsaikhan F⁵ ; Ahmad I⁶ ; Mahmood Saleh M⁷ ; Alamin Altoum A⁸ ; Aravindhan S⁹ ; Fakri Mustafa Y¹⁰ ; Mahmoudi R¹¹ ; Mohammadi A¹²
Source: International Immunopharmacology Published:2022

Abstract

A variety of mechanisms contribute to the occurrence and development of inflammatory atherosclerosis (IA), resulting in cardiovascular disease. PCSK9 (proprotein convertase subtilisin/ kexin type 9) has now been recognized as a key player in the pathophysiology of atherosclerosis. Following PCSK9 activation, LDL receptors (LDLR) are degraded and as a result, LDL cholesterol (LDLC) levels are increased. Increasing evidence reports that the PCSK9 axis mediates IA through different pathways, such as LDLR, LOX1, NF-kB, and TLR4. In recent years, PCSK9 pathway dysregulation has been identified as one of the fundamental mechanisms involved in IA. Recently, the importance of epigenetic factors, in particular, in non-coding RNAs, including miRNAs and long ncRNAs (lncRNAs) as well as circular RNAs (circRNAs) in the regulation of physiological and pathological events has received great attention. In this regard, an expanding body of research has revealed that different ncRNAs play important roles in the progression of inflammatory atherosclerosis through targeting genes related to the PCSK9 pathway at the post-transcriptional level. Of importance, the current study aimed to review the relationship between the various ncRNAs and PCSK9 pathway to identify the molecular mechanisms underlying IA pathogenesis as well as to introduce the novel PCSK9 pathway-related therapeutic interventions in combating IA. © 2022 Elsevier B.V.