Personalized statin therapy: Targeting metabolic processes to modulate the therapeutic and adverse effects of statins
Statins are widely used for treating lipid disorders and cardiovascular diseases. However, the therapeutic efficiency and adverse effects of statins vary among different patients, which numerous clinical and epidemiological studies have attributed to genetic polymorphisms in statin-metabolizing enzy...
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Elsevier
2025-01-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844025000088 |
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| author | Zhuangqi Shi Shuxin Han |
| author_facet | Zhuangqi Shi Shuxin Han |
| author_sort | Zhuangqi Shi |
| collection | DOAJ |
| description | Statins are widely used for treating lipid disorders and cardiovascular diseases. However, the therapeutic efficiency and adverse effects of statins vary among different patients, which numerous clinical and epidemiological studies have attributed to genetic polymorphisms in statin-metabolizing enzymes and transport proteins. The metabolic processes of statins are relatively complex, involving spontaneous or enzyme-catalyzed interconversion between more toxic lactone metabolites and active acid forms in the liver and bloodstream, influenced by multiple factors, including the expression levels of many metabolic enzymes and transporters. Addressing the variable statin therapeutic outcomes is a pressing clinical challenge. Transcription factors and epigenetic modifications regulate the metabolic enzymes and transporters involved in statin metabolism and disposition and, therefore, hold promise as 'personalized' targets for achieving optimized statin therapy. In this review, we explore the potential for customizing therapy by targeting the metabolism of statin medications. The biochemical bases of adverse reactions to statin drugs and their correlation with polymorphisms in metabolic enzymes and transporters are summarized. Next, we mainly focus on the regulatory roles of transcription factors and epigenetic modifications in regulating the gene expression of statin biochemical machinery. The recommendations for future therapies are finally proposed by targeting the central regulatory factors of statin metabolism. |
| format | Article |
| id | doaj-art-0290a78eab1e412f85d5289bcdb0a542 |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-0290a78eab1e412f85d5289bcdb0a5422025-01-17T04:51:47ZengElsevierHeliyon2405-84402025-01-01111e41629Personalized statin therapy: Targeting metabolic processes to modulate the therapeutic and adverse effects of statinsZhuangqi Shi0Shuxin Han1Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang, 830046, ChinaCorresponding author.; Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang, 830046, ChinaStatins are widely used for treating lipid disorders and cardiovascular diseases. However, the therapeutic efficiency and adverse effects of statins vary among different patients, which numerous clinical and epidemiological studies have attributed to genetic polymorphisms in statin-metabolizing enzymes and transport proteins. The metabolic processes of statins are relatively complex, involving spontaneous or enzyme-catalyzed interconversion between more toxic lactone metabolites and active acid forms in the liver and bloodstream, influenced by multiple factors, including the expression levels of many metabolic enzymes and transporters. Addressing the variable statin therapeutic outcomes is a pressing clinical challenge. Transcription factors and epigenetic modifications regulate the metabolic enzymes and transporters involved in statin metabolism and disposition and, therefore, hold promise as 'personalized' targets for achieving optimized statin therapy. In this review, we explore the potential for customizing therapy by targeting the metabolism of statin medications. The biochemical bases of adverse reactions to statin drugs and their correlation with polymorphisms in metabolic enzymes and transporters are summarized. Next, we mainly focus on the regulatory roles of transcription factors and epigenetic modifications in regulating the gene expression of statin biochemical machinery. The recommendations for future therapies are finally proposed by targeting the central regulatory factors of statin metabolism.http://www.sciencedirect.com/science/article/pii/S2405844025000088StatinAdverse effectsDrug metabolismHepatic uptakeDrug dispositionGene regulation |
| spellingShingle | Zhuangqi Shi Shuxin Han Personalized statin therapy: Targeting metabolic processes to modulate the therapeutic and adverse effects of statins Heliyon Statin Adverse effects Drug metabolism Hepatic uptake Drug disposition Gene regulation |
| title | Personalized statin therapy: Targeting metabolic processes to modulate the therapeutic and adverse effects of statins |
| title_full | Personalized statin therapy: Targeting metabolic processes to modulate the therapeutic and adverse effects of statins |
| title_fullStr | Personalized statin therapy: Targeting metabolic processes to modulate the therapeutic and adverse effects of statins |
| title_full_unstemmed | Personalized statin therapy: Targeting metabolic processes to modulate the therapeutic and adverse effects of statins |
| title_short | Personalized statin therapy: Targeting metabolic processes to modulate the therapeutic and adverse effects of statins |
| title_sort | personalized statin therapy targeting metabolic processes to modulate the therapeutic and adverse effects of statins |
| topic | Statin Adverse effects Drug metabolism Hepatic uptake Drug disposition Gene regulation |
| url | http://www.sciencedirect.com/science/article/pii/S2405844025000088 |
| work_keys_str_mv | AT zhuangqishi personalizedstatintherapytargetingmetabolicprocessestomodulatethetherapeuticandadverseeffectsofstatins AT shuxinhan personalizedstatintherapytargetingmetabolicprocessestomodulatethetherapeuticandadverseeffectsofstatins |