Pleiotropic Effects of PCSK9 Inhibitors on Cardio-Cerebrovascular Diseases
Cardiovascular disease (CVD) and ischemic stroke (IS) are the primary causes of mortality worldwide. Hypercholesterolemia has been recognized as an independent risk factor for CVD and IS. Numerous clinical trials have unequivocally demonstrated that reducing levels of low-density lipoprotein cholest...
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2024-11-01
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| author | Zhenzhen Li Lin Zhu Yeqiong Xu Yiting Zhang Yukai Liu Huiling Sun Shuo Li Meng Wang Teng Jiang Junshan Zhou Qiwen Deng |
| author_facet | Zhenzhen Li Lin Zhu Yeqiong Xu Yiting Zhang Yukai Liu Huiling Sun Shuo Li Meng Wang Teng Jiang Junshan Zhou Qiwen Deng |
| author_sort | Zhenzhen Li |
| collection | DOAJ |
| description | Cardiovascular disease (CVD) and ischemic stroke (IS) are the primary causes of mortality worldwide. Hypercholesterolemia has been recognized as an independent risk factor for CVD and IS. Numerous clinical trials have unequivocally demonstrated that reducing levels of low-density lipoprotein cholesterol (LDL-C) significantly mitigates the risk of both cardiac and cerebral vascular events, thereby enhancing patient prognosis. Consequently, LDL-C reduction remains a pivotal therapeutic strategy for CVD and IS. However, despite intensive statin therapy, a significant proportion of high-risk hypercholesterolemic patients fail to achieve sufficient reductions in LDL-C levels. In response to this challenge, an inhibitor targeting proprotein convertase subtilisin-kexin type 9 (PCSK9) has been developed as a therapeutic intervention for hyperlipidemia. Numerous randomized controlled trials (RCTs) have conclusively demonstrated that the combination of PCSK9 inhibitors and statins significantly enhances prognosis not only in patients with CVD, but also in those afflicted with symptomatic intracranial artery stenosis (sICAS). PCSK9 inhibitors significantly reduce LDL-C levels by binding to the PCSK9 molecule and preventing its interaction with LDLRs. This prevents degradation of the receptor and increases uptake of LDL-C, thereby decreasing its concentration in blood. Besides significantly reducing LDL-C levels, PCSK9 inhibitors also demonstrate anti-inflammatory and anti-atherosclerotic properties while promoting plaque stabilization and inhibiting platelet aggregation and thrombosis. This article aims to provide a comprehensive review based on the relevant literature regarding the evolving understanding of pleiotropic effects associated with PCSK9 inhibitors, particularly focusing on their impact on the cardiovascular system and central nervous system. |
| format | Article |
| id | doaj-art-7b5083416b8741e1b284dd7ff9ea20ab |
| institution | Kabale University |
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| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj-art-7b5083416b8741e1b284dd7ff9ea20ab2024-12-27T14:12:39ZengMDPI AGBiomedicines2227-90592024-11-011212272910.3390/biomedicines12122729Pleiotropic Effects of PCSK9 Inhibitors on Cardio-Cerebrovascular DiseasesZhenzhen Li0Lin Zhu1Yeqiong Xu2Yiting Zhang3Yukai Liu4Huiling Sun5Shuo Li6Meng Wang7Teng Jiang8Junshan Zhou9Qiwen Deng10Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, ChinaDepartment of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, ChinaCentral Laboratory of Changshu Medical Examination Institute, Changshu 215500, ChinaDepartment of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, ChinaDepartment of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, ChinaGeneral Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, ChinaDepartment of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, ChinaDepartment of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, ChinaDepartment of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, ChinaDepartment of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, ChinaDepartment of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, ChinaCardiovascular disease (CVD) and ischemic stroke (IS) are the primary causes of mortality worldwide. Hypercholesterolemia has been recognized as an independent risk factor for CVD and IS. Numerous clinical trials have unequivocally demonstrated that reducing levels of low-density lipoprotein cholesterol (LDL-C) significantly mitigates the risk of both cardiac and cerebral vascular events, thereby enhancing patient prognosis. Consequently, LDL-C reduction remains a pivotal therapeutic strategy for CVD and IS. However, despite intensive statin therapy, a significant proportion of high-risk hypercholesterolemic patients fail to achieve sufficient reductions in LDL-C levels. In response to this challenge, an inhibitor targeting proprotein convertase subtilisin-kexin type 9 (PCSK9) has been developed as a therapeutic intervention for hyperlipidemia. Numerous randomized controlled trials (RCTs) have conclusively demonstrated that the combination of PCSK9 inhibitors and statins significantly enhances prognosis not only in patients with CVD, but also in those afflicted with symptomatic intracranial artery stenosis (sICAS). PCSK9 inhibitors significantly reduce LDL-C levels by binding to the PCSK9 molecule and preventing its interaction with LDLRs. This prevents degradation of the receptor and increases uptake of LDL-C, thereby decreasing its concentration in blood. Besides significantly reducing LDL-C levels, PCSK9 inhibitors also demonstrate anti-inflammatory and anti-atherosclerotic properties while promoting plaque stabilization and inhibiting platelet aggregation and thrombosis. This article aims to provide a comprehensive review based on the relevant literature regarding the evolving understanding of pleiotropic effects associated with PCSK9 inhibitors, particularly focusing on their impact on the cardiovascular system and central nervous system.https://www.mdpi.com/2227-9059/12/12/2729pleiotropic effectsproprotein convertase subtilisin-kexin type 9central nervous systemcardiovascular systemlipid metabolismatherosclerosis |
| spellingShingle | Zhenzhen Li Lin Zhu Yeqiong Xu Yiting Zhang Yukai Liu Huiling Sun Shuo Li Meng Wang Teng Jiang Junshan Zhou Qiwen Deng Pleiotropic Effects of PCSK9 Inhibitors on Cardio-Cerebrovascular Diseases Biomedicines pleiotropic effects proprotein convertase subtilisin-kexin type 9 central nervous system cardiovascular system lipid metabolism atherosclerosis |
| title | Pleiotropic Effects of PCSK9 Inhibitors on Cardio-Cerebrovascular Diseases |
| title_full | Pleiotropic Effects of PCSK9 Inhibitors on Cardio-Cerebrovascular Diseases |
| title_fullStr | Pleiotropic Effects of PCSK9 Inhibitors on Cardio-Cerebrovascular Diseases |
| title_full_unstemmed | Pleiotropic Effects of PCSK9 Inhibitors on Cardio-Cerebrovascular Diseases |
| title_short | Pleiotropic Effects of PCSK9 Inhibitors on Cardio-Cerebrovascular Diseases |
| title_sort | pleiotropic effects of pcsk9 inhibitors on cardio cerebrovascular diseases |
| topic | pleiotropic effects proprotein convertase subtilisin-kexin type 9 central nervous system cardiovascular system lipid metabolism atherosclerosis |
| url | https://www.mdpi.com/2227-9059/12/12/2729 |
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