PCSK9: A Key Target for the Treatment of Cardiovascular Disease (CVD)
Proprotein convertase subtilisin/kexin type 9 (PCSK9), as a vital modulator of low-density lipoprotein cholesterol (LDL-C) , is raised in hepatocytes and released into plasma where it binds to LDL receptors (LDLR), leading to their cleavage. PCSK9 adheres to the epidermal growth factor-like repeat A...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Tabriz University of Medical Sciences
2020-08-01
|
| Series: | Advanced Pharmaceutical Bulletin |
| Subjects: | |
| Online Access: | https://apb.tbzmed.ac.ir/PDF/apb-10-502.pdf |
| _version_ | 1819028632765464576 |
|---|---|
| author | Saeideh Sobati Amir Shakouri Mahdi Edalati Daryoush Mohammadnejad Reza Parvan Javad Masoumi Jalal Abdolalizadeh |
| author_facet | Saeideh Sobati Amir Shakouri Mahdi Edalati Daryoush Mohammadnejad Reza Parvan Javad Masoumi Jalal Abdolalizadeh |
| author_sort | Saeideh Sobati |
| collection | DOAJ |
| description | Proprotein convertase subtilisin/kexin type 9 (PCSK9), as a vital modulator of low-density lipoprotein cholesterol (LDL-C) , is raised in hepatocytes and released into plasma where it binds to LDL receptors (LDLR), leading to their cleavage. PCSK9 adheres to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR which is confirmed by crystallography. LDLR expression is adjusted at the transcriptional level through sterol regulatory element binding protein 2 (SREBP-2) and at the post translational stages, specifically through PCSK9, and the inducible degrader of the LDLR PCSK9 inhibition is an appealing new method for reducing the concentration of LDL-C. In this review the role of PCSK9 in lipid homeostasis was elucidated, the effect of PCSK9 on atherosclerosis was highlighted, and contemporary therapeutic techniques that focused on PCSK9 were summarized. Several restoration methods to inhibit PCSK9 have been proposed which concentrate on both extracellular and intracellular PCSK9, and they include blockage of PCSK9 production by using gene silencing agents and blockage of it’s binding to LDLR through antibodies and inhibition of PCSK9 autocatalytic processes by tiny molecule inhibitors. |
| first_indexed | 2024-12-21T06:01:27Z |
| format | Article |
| id | doaj.art-98276016d8b44b4b982b0c950dd650e6 |
| institution | Directory Open Access Journal |
| issn | 2228-5881 2251-7308 |
| language | English |
| last_indexed | 2024-12-21T06:01:27Z |
| publishDate | 2020-08-01 |
| publisher | Tabriz University of Medical Sciences |
| record_format | Article |
| series | Advanced Pharmaceutical Bulletin |
| spelling | doaj.art-98276016d8b44b4b982b0c950dd650e62022-12-21T19:13:45ZengTabriz University of Medical SciencesAdvanced Pharmaceutical Bulletin2228-58812251-73082020-08-0110450251110.34172/apb.2020.062apb-28357PCSK9: A Key Target for the Treatment of Cardiovascular Disease (CVD)Saeideh Sobati0Amir Shakouri1Mahdi Edalati2Daryoush Mohammadnejad3Reza Parvan4Javad Masoumi5Jalal Abdolalizadeh6Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.Department of Biosciences, University of Milan, Via celoria 26, 20133, Milan, Italy.Immunology Department, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.Proprotein convertase subtilisin/kexin type 9 (PCSK9), as a vital modulator of low-density lipoprotein cholesterol (LDL-C) , is raised in hepatocytes and released into plasma where it binds to LDL receptors (LDLR), leading to their cleavage. PCSK9 adheres to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR which is confirmed by crystallography. LDLR expression is adjusted at the transcriptional level through sterol regulatory element binding protein 2 (SREBP-2) and at the post translational stages, specifically through PCSK9, and the inducible degrader of the LDLR PCSK9 inhibition is an appealing new method for reducing the concentration of LDL-C. In this review the role of PCSK9 in lipid homeostasis was elucidated, the effect of PCSK9 on atherosclerosis was highlighted, and contemporary therapeutic techniques that focused on PCSK9 were summarized. Several restoration methods to inhibit PCSK9 have been proposed which concentrate on both extracellular and intracellular PCSK9, and they include blockage of PCSK9 production by using gene silencing agents and blockage of it’s binding to LDLR through antibodies and inhibition of PCSK9 autocatalytic processes by tiny molecule inhibitors.https://apb.tbzmed.ac.ir/PDF/apb-10-502.pdfatherosclerosischolesterolcoronary heart diseaseldlmonoclonal antibodypcsk9 |
| spellingShingle | Saeideh Sobati Amir Shakouri Mahdi Edalati Daryoush Mohammadnejad Reza Parvan Javad Masoumi Jalal Abdolalizadeh PCSK9: A Key Target for the Treatment of Cardiovascular Disease (CVD) Advanced Pharmaceutical Bulletin atherosclerosis cholesterol coronary heart disease ldl monoclonal antibody pcsk9 |
| title | PCSK9: A Key Target for the Treatment of Cardiovascular Disease (CVD) |
| title_full | PCSK9: A Key Target for the Treatment of Cardiovascular Disease (CVD) |
| title_fullStr | PCSK9: A Key Target for the Treatment of Cardiovascular Disease (CVD) |
| title_full_unstemmed | PCSK9: A Key Target for the Treatment of Cardiovascular Disease (CVD) |
| title_short | PCSK9: A Key Target for the Treatment of Cardiovascular Disease (CVD) |
| title_sort | pcsk9 a key target for the treatment of cardiovascular disease cvd |
| topic | atherosclerosis cholesterol coronary heart disease ldl monoclonal antibody pcsk9 |
| url | https://apb.tbzmed.ac.ir/PDF/apb-10-502.pdf |
| work_keys_str_mv | AT saeidehsobati pcsk9akeytargetforthetreatmentofcardiovasculardiseasecvd AT amirshakouri pcsk9akeytargetforthetreatmentofcardiovasculardiseasecvd AT mahdiedalati pcsk9akeytargetforthetreatmentofcardiovasculardiseasecvd AT daryoushmohammadnejad pcsk9akeytargetforthetreatmentofcardiovasculardiseasecvd AT rezaparvan pcsk9akeytargetforthetreatmentofcardiovasculardiseasecvd AT javadmasoumi pcsk9akeytargetforthetreatmentofcardiovasculardiseasecvd AT jalalabdolalizadeh pcsk9akeytargetforthetreatmentofcardiovasculardiseasecvd |