PCSK9/LDLR System and Rheumatoid Arthritis-Related Atherosclerosis

Arida, Aikaterini; Legaki, Aigli‐Ioanna; Kravvariti, Evrydiki; Protogerou, Athanasios; Sfikakis, Petros P.; Chatzigeorgiou, Antonios

doi:10.3389/fcvm.2021.738764

Cited by 14 publications

(11 citation statements)

References 33 publications

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“…Other novel markers found to be associated with accelerated atherosclerosis in RA patients were von Willebrand factor (vWF), 101 cellular communication network factor 1 (CCN1), 98 human endothelial cell-specific molecule-1 (endocan), 70 PCSK9/LDLR system, 94 and oxLDL. 67 , 82 Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is a biomarker used to assess vascular inflammation.…”

Section: Discussionmentioning

confidence: 99%

Accelerated atherosclerosis in rheumatoid arthritis: a systematic review

Thomas

Gorantla

2022

F1000Res

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Background: Rheumatoid arthritis (RA) is a highly prevalent, chronic inflammatory condition of the synovial joints that affects approximately 1% of the global population. The pathogenesis of RA is predominantly inflammatory in nature, thereby accelerating the co-occurrence of other immunoinflammatory conditions such as atherosclerosis. Apart from traditional cardiovascular risk factors, RA patients possess a multitude of other factors that predispose them to early atherosclerotic disease. The aim of this systematic review is to assess the prevalence of premature atherosclerosis in RA patients and elucidate the role that proinflammatory cytokines, neutrophil extracellular traps, RA-related autoantibodies, and endothelial dysfunction play in the pathophysiology of RA-mediated atherosclerosis. We also discussed novel biomarkers that can be used to predict early atherosclerosis in RA. Methods: This review followed the PRISMA guidelines to select and analyze relevant articles. A literature search for articles was performed on February 25, 2022, through three research databases including PubMed, ProQuest, and ScienceDirect. The query used to identify relevant publications was “Rheumatoid arthritis and atherosclerosis” and the search duration was set from 2011-2022. Relevant articles were selected based on the inclusion and exclusion criteria. Results: Our initial search generated 21,235 articles. We narrowed our search according to the inclusion and exclusion criteria. After assessing eligibility based on the full content of the articles, 73 articles were ultimately chosen for this review. Conclusion: There is a high prevalence of accelerated atherosclerosis among RA patients. We found evidence to explain the role of proinflammatory cytokines, neutrophil extracellular traps, RA-related autoantibodies, and endothelial dysfunction in the pathophysiology RA-mediated atherosclerosis. Therapies targeting either the inflammatory load or traditional CV risk-factors seem to improve vascular outcomes in RA patients. Novel markers of atherosclerosis in RA may be useful in predicting premature atherosclerosis and serve as new targets for therapeutic intervention.

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Section: Discussionmentioning

confidence: 99%

Accelerated atherosclerosis in rheumatoid arthritis: a systematic review

Thomas

Gorantla

2022

F1000Res

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“…Similarly, transgenic pigs with the D374Y gain-of-function mutation in the PCSK9 gene are more prone to develop atherosclerosis than WT pigs when fed a highfat and high-cholesterol diet (121). In patients with rheumatoid arthritis (RA), the plasma level of PCSK9 and the ratio of PCSK9 to LDLR are positively correlated with the occurrence and development of atherosclerosis (122). LRP5 and LRP6, as coreceptors of PCSK9, promote atherosclerosis by activating the Wnt/β-catenin signaling pathway, resulting in significant proliferation of VSMCs and decreased anti-inflammatory macrophages (78,81).…”

Section: Pcsk9 and Atherosclerosismentioning

confidence: 99%

Effect of PCSK9 on atherosclerotic cardiovascular diseases and its mechanisms: Focus on immune regulation

Chao-zhen²,

Liu³

2023

Front. Cardiovasc. Med.

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Atherosclerosis is a basic pathological characteristic of many cardiovascular diseases, and if not effectively treated, patients with such disease may progress to atherosclerotic cardiovascular diseases (ASCVDs) and even heart failure. The level of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) is significantly higher in patients with ASCVDs than in the healthy population, suggesting that it may be a promising new target for the treatment of ASCVDs. PCSK9 produced by the liver and released into circulation inhibits the clearance of plasma low-density lipoprotein-cholesterol (LDL-C), mainly by downregulating the level of LDL-C receptor (LDLR) on the surface of hepatocytes, leading to upregulated LDL-C in plasma. Numerous studies have revealed that PCSK9 may cause poor prognosis of ASCVDs by activating the inflammatory response and promoting the process of thrombosis and cell death independent of its lipid-regulatory function, yet the underlying mechanisms still need to be further clarified. In patients with ASCVDs who are intolerant to statins or whose plasma LDL-C levels fail to descend to the target value after treatment with high-dose statins, PCSK9 inhibitors often improve their clinical outcomes. Here, we summarize the biological characteristics and functional mechanisms of PCSK9, highlighting its immunoregulatory function. We also discuss the effects of PCSK9 on common ASCVDs.

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“…Other novel markers found to be associated with accelerated atherosclerosis in RA patients were von Willebrand factor (vWF), 101 cellular communication network factor 1 (CCN1), 98 human endothelial cell-specific molecule-1 (endocan), 70 PCSK9/LDLR system, 94 and oxLDL. 67,82 Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is a biomarker used to assess vascular inflammation.…”

Section: The Role Of Endothelial Dysfunctionmentioning

confidence: 99%

Accelerated atherosclerosis in rheumatoid arthritis: a systematic review

Gorantla

Thomas²

2023

F1000Res

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Background: Rheumatoid arthritis (RA) is a highly prevalent, chronic inflammatory condition of the synovial joints that affects approximately 1% of the global population. The pathogenesis of RA is predominantly inflammatory in nature, thereby accelerating the co-occurrence of other immunoinflammatory conditions such as atherosclerosis. Apart from traditional cardiovascular risk factors, RA patients possess a multitude of other factors that predispose them to early atherosclerotic disease. The aim of this systematic review is to assess the prevalence of premature atherosclerosis in RA patients and elucidate the role that proinflammatory cytokines, RA-related autoantibodies, and endothelial dysfunction play in the pathophysiology of RA-mediated atherosclerosis. We also discussed novel biomarkers that can be used to predict early atherosclerosis in RA and current guidelines used to treat RA. Methods: This review followed the PRISMA guidelines to select and analyze relevant articles. A literature search for articles was performed on February 25, 2022, through three research databases including PubMed, ProQuest, and ScienceDirect. The query used to identify relevant publications was “Rheumatoid arthritis and atherosclerosis” and the search duration was set from 2012-2022. Relevant articles were selected based on the inclusion and exclusion criteria. Results: Our initial search generated 21,235 articles. We narrowed our search according to the inclusion and exclusion criteria. After assessing eligibility based on the full content of the articles, 73 articles were ultimately chosen for this review. Conclusion: There is an increased prevalence of accelerated atherosclerosis among RA patients. We found evidence to explain the role of proinflammatory cytokines, RA-related autoantibodies, and endothelial dysfunction in the pathophysiology RA-mediated atherosclerosis. Therapies targeting either the inflammatory load or traditional CV risk-factors seem to improve vascular outcomes in RA patients. Novel markers of atherosclerosis in RA may be useful in predicting premature atherosclerosis and serve as new targets for therapeutic intervention.

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PCSK9/LDLR System and Rheumatoid Arthritis-Related Atherosclerosis

Cited by 14 publications

References 33 publications

Accelerated atherosclerosis in rheumatoid arthritis: a systematic review

Accelerated atherosclerosis in rheumatoid arthritis: a systematic review

Effect of PCSK9 on atherosclerotic cardiovascular diseases and its mechanisms: Focus on immune regulation

Accelerated atherosclerosis in rheumatoid arthritis: a systematic review

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