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

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          Abstract

          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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          Most cited references163

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          Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease.

          Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved.
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            Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease

            Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain.
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              Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol

              Inclisiran inhibits hepatic synthesis of proprotein convertase subtilisin-kexin type 9. Previous studies suggest that inclisiran might provide sustained reductions in low-density lipoprotein (LDL) cholesterol levels with infrequent dosing.
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                Author and article information

                Journal
                Int J Mol Med
                Int J Mol Med
                IJMM
                International Journal of Molecular Medicine
                D.A. Spandidos
                1107-3756
                1791-244X
                June 2024
                10 May 2024
                10 May 2024
                : 53
                : 6
                : 57
                Affiliations
                [1 ]Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100191, P.R. China
                [2 ]Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, P.R. China
                [3 ]Department of Pharmacy, Peking University First Hospital, Beijing 100034, P.R. China
                [4 ]Department of Hematology, Peking University First Hospital, Beijing 100034, P.R. China
                Author notes
                Correspondence to: Professor Qian Xiang or Professor Yimin Cui, Institute of Clinical Pharmacology, Peking University First Hospital, 38 Xueyuan Road, Haidian, Beijing 100191, P.R. China, E-mail: xiangqz@ 123456pkufh.com , E-mail: cui.pharm@ 123456pkufh.com
                [*]

                Contributed equally

                Article
                ijmm-53-06-05381
                10.3892/ijmm.2024.5381
                11093556
                708f603c-002a-4716-9b08-599663fe9597
                Copyright: © 2024 Chong et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 10 January 2024
                : 22 April 2024
                Funding
                Funded by: National Key Research and Development Program of China
                Award ID: 2021YFC2500500
                Award ID: 2021YFC2500503
                Funded by: National High Level Hospital Clinical Research Funding (Scientific Research Fund of Peking University First Hospital
                Award ID: 2022SF15
                Funded by: National Natural Science Foundation of China General Program
                Award ID: 82073935
                Award ID: 82373950
                The present study was supported by the National Key Research and Development Program of China (grant nos. 2021YFC2500500 and 2021YFC2500503), the National High Level Hospital Clinical Research Funding (Scientific Research Fund of Peking University First Hospital (grant no. 2022SF15), and the National Natural Science Foundation of China General Program (grant nos. 82073935 and 82373950).
                Categories
                Review

                proprotein convertase subtilisin kexin type 9,thrombosis,haemostasis,metabolic states

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