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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
Authors
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Authors Affiliations
  1. 1. Department of Radiological Techniques, Al-Mustaqbal University College, Babylon, Hillah, 51001, Iraq
  2. 2. Iraqi Ministry of Education, Baghdad, Iraq
  3. 3. Veterinary medicine college, Al-Qasim green University, Al-Qasim, Iraq
  4. 4. Department of Pathologic physiology, Samarkand State Medical University, Samarkand, Uzbekistan
  5. 5. College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia
  6. 6. Department of Medical Rehabilitation Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
  7. 7. Department of Biophysics, College of Applied Sciences, University Of Anbar, Anbar, Iraq
  8. 8. Department of Medical Laboratory Sciences, College of Health Sciences, Gulf Medical University, Ajman, United Arab Emirates
  9. 9. Department of Pharmacology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, India
  10. 10. Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul, 41001, Iraq
  11. 11. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  12. 12. Department of Clinical Biochemistry, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

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.
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