PCSK9 pathway-noncoding RNAs crosstalk: Emerging opportunities for novel therapeutic approaches in inflammatory atherosclerosis

Al-Awsi, Ghaidaa Raheem Lateef; Lafta, Methaq Hadi; Kzar, Hamzah H.; Samieva, G.U.; Alsaikhan, Fahad; Ahmad, I.; Saleh, Marwan Mahmood; Altoum, Abdelgadir Alamin; Aravindhan, Surendar; Mustafa, Yasser Fakri; Mahmoudi, Reza; Mohammadi, Asgar

doi:10.1016/j.intimp.2022.109318

Cited by 6 publications

(4 citation statements)

References 146 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Anti-inflammatory therapy can significantly reduce the risk of recurrent cardiovascular events without affecting lipid levels in patients with previous myocardial infarction ( 84 ). The PCSK9 pathway promotes the inflammatory response and plays a role in in the thrombosis and atherosclerosis processes ( 85 , 86 ).…”

Section: Mechanisms Of Pcsk9 In Thrombosis and Haemostasismentioning

confidence: 99%

Effects of PCSK9 on thrombosis and haemostasis in a variety of metabolic states: Lipids and beyond (Review)

Chong,

Mu,

Cen

et al. 2024

Int J Mol Med

View full text Add to dashboard Cite

Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors are widely recognised as being able to induce a potent reduction in low-density lipoprotein-cholesterol. An increasing number of studies have suggested that PCSK9 also influences the haemostatic system by altering platelet function and the coagulation cascade. These findings have significant implications for anti-PCSK9 therapy in patients with specific coagulation conditions, including expanded indications, dose adjustments and drug interactions. The present review summarises the changes in PCSK9 levels in individuals with liver diseases, chronic kidney diseases, diabetes mellitus, cancer and other disease states, and discusses their impact on thrombosis and haemostasis. Furthermore, the structure, effects and regulatory mechanisms of PCSK9 on platelets, coagulation factors, inflammatory cells and endothelial cells during coagulation and haemostasis are described.

show abstract

Section: Mechanisms Of Pcsk9 In Thrombosis and Haemostasismentioning

confidence: 99%

Effects of PCSK9 on thrombosis and haemostasis in a variety of metabolic states: Lipids and beyond (Review)

Chong,

Mu,

Cen

et al. 2024

Int J Mol Med

View full text Add to dashboard Cite

show abstract

“…Additionally, the histone acetyltransferase P300 may increase PCSK9 expression (140). Non-coding RNAs (ncRNA) play a crucial role in the progression of inflammation in atherosclerosis by targeting genes related to the PCSK9 pathway at the post-transcriptional level (141). Further research is needed to uncover the pathway-related mechanisms of PCSK9 in AAA, potentially providing new insights and breakthroughs into the complex pathogenesis of AAA.…”

Section: Pcsksmentioning

confidence: 99%

Epigenetic modifications in abdominal aortic aneurysms: from basic to clinical

Liu,

Sun,

Gou

et al. 2024

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Abdominal Aortic Aneurysm (AAA) is a disease characterized by localized dilation of the abdominal aorta, involving multiple factors in its occurrence and development, ultimately leading to vessel rupture and severe bleeding. AAA has a high mortality rate, and there is a lack of targeted therapeutic drugs. Epigenetic regulation plays a crucial role in AAA, and the treatment of AAA in the epigenetic field may involve a series of related genes and pathways. Abnormal expression of these genes may be a key factor in the occurrence of the disease and could potentially serve as promising therapeutic targets. Understanding the epigenetic regulation of AAA is of significant importance in revealing the mechanisms underlying the disease and identifying new therapeutic targets. This knowledge can contribute to offering AAA patients better clinical treatment options beyond surgery. This review systematically explores various aspects of epigenetic regulation in AAA, including DNA methylation, histone modification, non-coding RNA, and RNA modification. The analysis of the roles of these regulatory mechanisms, along with the identification of relevant genes and pathways associated with AAA, is discussed comprehensively. Additionally, a comprehensive discussion is provided on existing treatment strategies and prospects for epigenetics-based treatments, offering insights for future clinical interventions.

show abstract

“…Atherosclerosis is a chronic inflammatory disease and inflammation is involved in the pathophysiological process of atherosclerosis. 31 In the initial stages, ox-LDL represents the main initiator, and its cytotoxic effect can damage vascular endothelial cells directly, leading to changes in endothelial permeability, resulting in the passage of lipids and cellular components through the damaged endothelium and their subsequent deposition in the intima. Furthermore, the oxidation of low-density lipoprotein cholesterol (LDL-c), as well as the influence of monocyte chemotactic protein 1 and platelet-derived growth factor, alters the lymphocyte and monocyte composition of the overall blood leukocyte content within the damaged skin adhesion, leading to aggregation and leukocyte adhesion under the influence of inflammatory cytokines in the blood vessels, resulting in chronic inflammation.…”

Section: Factors Affecting the Stability Of Atherosclerotic Plaquementioning

confidence: 99%

Potential new therapeutic targets: Association of microRNA with atherosclerotic plaque stability

Huang

2023

Int J Immunopathol Pharmacol

View full text Add to dashboard Cite

Cardiovascular disease represents a major threat to human health with vascular atherosclerosis contributing significantly to its cause, particularly due to the ease of rupture of atherosclerotic plaques. The stability of atherosclerotic plaques is influenced by a variety of factors, including intraplaque neovascularization, the inflammatory response, smooth muscle cells and macrophages, and core lipid volumes. Thus, the investigation of factors affecting the stability of atherosclerotic plaques is of great significance for the development of new drugs for the treatment of atherosclerotic diseases. MicroRNAs are small single-stranded non-coding RNAs between 17 and 22 nucleotides in length. They are translated together with the untranslated region (UTR) of the target gene mRNA, where the completeness of base-pairing can influence the translation or degradation of the target genes. MicroRNAs can thus regulate gene expression at the post-transcriptional level and have been demonstrated to be extensively involved in the regulation of various factors affecting plaque stability. In this paper, we review microRNA development, factors affecting atherosclerotic plaque stability, and the relationship between microRNAs and plaque stability, with the aim of describing the mechanisms by which microRNAs affect gene and protein expression in relation to atherosclerosis progression (including plaque rupture) to suggest new therapeutic targets for atherosclerotic disease.

show abstract

PCSK9 pathway-noncoding RNAs crosstalk: Emerging opportunities for novel therapeutic approaches in inflammatory atherosclerosis

Cited by 6 publications

References 146 publications

Effects of PCSK9 on thrombosis and haemostasis in a variety of metabolic states: Lipids and beyond (Review)

Effects of PCSK9 on thrombosis and haemostasis in a variety of metabolic states: Lipids and beyond (Review)

Epigenetic modifications in abdominal aortic aneurysms: from basic to clinical

Potential new therapeutic targets: Association of microRNA with atherosclerotic plaque stability

Contact Info

Product

Resources

About