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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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The accumulating evidence revealed that microbiota plays a significant function in training, function, and the induction of host immunity. Once this interaction (immune system-microbiota) works correctly, it enables the production of protective responses against pathogens and keeps the regulatory pathways essential for maintaining tolerance to innocent antigens. This concept of immunity and metabolic activity redefines the realm of immunometabolism, paving the way for innovative therapeutic interventions to modulate immune cells through immune metabolic alterations. A body of evidence suggests that microbiota-derived metabolites, including short-chain fatty acids (SCFAs) such as butyrate, acetate, and propionate, play a key role in immune balance. SCFAs act on many cell types to regulate various vital biological processes, including host metabolism, intestinal function, and the immune system. Such SCFAs generated by gut bacteria also impact immunity, cellular function, and immune cell fate. This is a new concept of immune metabolism, and better knowledge about how lifestyle affects intestinal immunometabolism is crucial for preventing and treating disease. In this review article, we explicitly focus on the function of SCFAs in the metabolism of immune cells, especially macrophages, neutrophils, dendritic cells (DCs), B cells, T (Th) helper cells, and cytotoxic T cells (CTLs)., (Copyright © 2022 Elsevier B.V. All rights reserved.)