Molecular and cellular biology of PCSK9: impact on glucose homeostasis

Tchéoubi, Sègbédé E R; Akpovi, Casimir D.; Coppée, Frédérique; Declèves, Anne‐Emilie; Laurent, Sophie; Agbangla, Clément; Burtéa, Carmen

doi:10.1080/1061186x.2022.2092622

Cited by 11 publications

(7 citation statements)

References 163 publications

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“…PCSK9 inhibitors are now used in the clinics and are well tolerated. Interestingly, genetic variants in PCSK9 that mimic the effect of PCSK9 inhibitors are associated with increased risk for type 2 diabetes (T2D) development, raising the possibility that long-term PCSK9 inhibition may result in new-onset T2D ( 62 , 63 , 64 , 65 ). Although this view has been challenged by many trials using anti-PCSK9 antibodies ( 66 , 67 ), a recent meta-analysis of randomized clinical trials of PCSK9 inhibitors reported a modest increase in plasma glucose and HbA1C with anti-PCSK9 antibodies ( 68 ).…”

Section: Discussionmentioning

confidence: 99%

Geranylgeranyl isoprenoids and hepatic Rap1a regulate basal and statin-induced expression of PCSK9

Wang,

Tinsley,

Spolitu

et al. 2024

Journal of Lipid Research

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Section: Discussionmentioning

confidence: 99%

Geranylgeranyl isoprenoids and hepatic Rap1a regulate basal and statin-induced expression of PCSK9

Wang,

Tinsley,

Spolitu

et al. 2024

Journal of Lipid Research

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“…Specifically, PCSK9 interacts with human pancreatic β-cells through LDLR and an intracellular signalling mechanism that regulates the expression of CD36, anti-programmed death 1 and HLA-ABC receptors ( 141 ). It remains unclear whether the use of PCSK9 inhibitors increases the risk of developing diabetes ( 143 , 144 ). Considering the inconsistent results, further investigations are required to elucidate the association between PCSK9 levels and diabetes.…”

Section: Roles Of Pcsk9 In Thrombosis and Haemostasis Under Disease S...mentioning

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

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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.

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“…Therefore, several PCSK9 LOF variants have been reported in literature with different effects on glucose homeostasis and many controversies exist ( 78 ). Some variants result in a significant increase in glucose levels and higher risk of type 2 diabetes, other variants do not cause alteration of glucose metabolism ( 74 ).…”

Section: Agnostic Evaluation Of Pcsk9 Effects By Proteomics and Lipid...mentioning

confidence: 99%

“…Similarly, impairment of glucose metabolism is also variable in human subjects carrying PCSK9 LOF variants, an effect depending on the genetic background of the studied population, in which the risk to develop diabetes is also associated to the individual degree of functional loss (77). Therefore, several PCSK9 LOF variants have been reported in literature with different effects on glucose homeostasis and many controversies exist (78). Some variants result in a significant increase in glucose levels and higher risk of type 2 diabetes, other variants do not cause alteration of glucose metabolism (74).…”

Section: Pcsk9 and New-onset Diabetesmentioning

confidence: 99%

Proteomics and Lipidomics to unveil the contribution of PCSK9 beyond cholesterol lowering: a narrative review

Gianazza

Macchi

Banfi

et al. 2023

Front. Cardiovasc. Med.

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Proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the key regulators of the low-density lipoprotein receptor (LDLR), can play a direct role in atheroma development. Although advances in the understandings of genetic PCSK9 polymorphisms have enabled to reveal the role of PCSK9 in the complex pathophysiology of cardiovascular diseases (CVDs), increasing lines of evidence support non-cholesterol-related processes mediated by PCSK9. Owing to major improvements in mass spectrometry-based technologies, multimarker proteomic and lipidomic panels hold the promise to identify novel lipids and proteins potentially related to PCSK9. Within this context, this narrative review aims to provide an overview of the most significant proteomics and lipidomics studies related to PCSK9 effects beyond cholesterol lowering. These approaches have enabled to unveil non-common targets of PCSK9, potentially leading to the development of novel statistical models for CVD risk prediction. Finally, in the era of precision medicine, we have reported the impact of PCSK9 on extracellular vesicles (EVs) composition, an effect that could contribute to an increased prothrombotic status in CVD patients. The possibility to modulate EVs release and cargo could help counteract the development and progression of the atherosclerotic process.

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Molecular and cellular biology of PCSK9: impact on glucose homeostasis

Cited by 11 publications

References 163 publications

Geranylgeranyl isoprenoids and hepatic Rap1a regulate basal and statin-induced expression of PCSK9

Geranylgeranyl isoprenoids and hepatic Rap1a regulate basal and statin-induced expression of PCSK9

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

Proteomics and Lipidomics to unveil the contribution of PCSK9 beyond cholesterol lowering: a narrative review

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