4.5 Article

Impact of dyslipidemia in the development of cardiovascular complications: Delineating the potential therapeutic role of coenzyme

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BIOCHIMIE
卷 204, 期 -, 页码 33-40

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ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biochi.2022.08.018

关键词

Type 2 diabetes; Dyslipidemia; Cardiovascular disease; Statins; Mevalonate pathway; Coenzyme Q 10

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Dyslipidemia is a major risk factor for cardiovascular disease in type 2 diabetes patients. Statin drugs can lower cholesterol and reduce the risk of CVD. However, statins also inhibit the synthesis of coenzyme Q10, which is crucial for mitochondrial function and antioxidant properties. Therefore, researchers are exploring alternative approaches to block cholesterol synthesis while maintaining CoQ10 levels to protect against the destructive complications of dyslipidemia.
Dyslipidemia is one of the major risk factors for the development of cardiovascular disease (CVD) in patients with type 2 diabetes (T2D). This metabolic anomality is implicated in the generation of oxidative stress, an inevitable process involved in destructive mechanisms leading to myocardial damage. Fortunately, commonly used drugs like statins can counteract the detrimental effects of dyslipidemia by lowering cholesterol to reduce CVD-risk in patients with T2D. Statins mainly function by blocking the production of cholesterol by targeting the mevalonate pathway. However, by blocking cholesterol synthesis, statins coincidently inhibit the synthesis of other essential isoprenoid intermediates of the mevalonate pathway like farnesyl pyrophosphate and coenzyme Q10 (CoQ10). The latter is by far the most important co-factor and co-enzyme required for efficient mitochondrial oxidative capacity, in addition to its robust antioxidant properties. In fact, supplementation with CoQ10 has been found to be beneficial in ameliorating oxidative stress and improving blood flow in subjects with mild dyslipidemia.. Beyond discussing the destructive effects of oxidative stress in dyslipidemia-induced CVD-related complications, the current review brings a unique perspective in exploring the mevalonate pathway to block cholesterol synthesis while enhancing or maintaining CoQ10 levels in conditions of dyslipidemia. Furthermore, this review disscusses the therapeutic potential of bioactive compounds in targeting the downstream of the mevalonate pathway, more importantly, their ability to block cholesterol while maintaining CoQ10 biosynthesis to protect against the destructive complications of dyslipidemia.(c) 2022 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.

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