Abstract
Dyslipidemia is one of the main risk factors leading to atherosclerotic cardiovascular disease (CVD). According to recent treatment guidelines, subjects at substantial risk of CVD should meet more aggressive targets for low-density lipoprotein(LDL)- cholesterol levels. Treatment with statins fails to protect a significant percentage of patients from cardiovascular events despite efficient cholesterol-lowering. Moreover, clinical and epidemiologic data highlight the need of therapies to reduce the residual cardiovascular risk associated with low high-density lipoprotein(HDL)-cholesterol and elevated triglyceride levels. There are several novel agents undergoing preclinical or clinical development for the treatment of dyslipidemia. Squalene synthase inhibitors, antisense oligonucleotides targeting the production of apolipoprotein(apo)B-100, inhibitors of proprotein convertase subtilisin/kexin type 9, microsomal triglyceride transfer protein inhibitors, peroxisome proliferator-activated receptor agonists, and thyroid hormone receptor agonists are some of the alternative approaches for lipid-lowering. Moreover, HDL-targeted therapies such as the cholesteryl ester transfer protein inhibitors, HDLderived proteins, and mimetic peptides/lipids can increase HDL-cholesterol levels or improve the antiatherosclerotic properties of HDL. In conclusion, the emergence of agents that act in monotherapy or in combination with available lipid-modifying drugs may allow more effective management of dyslipidemia and, consequently, reduce the burden of CVD.
Keywords: Antisense oligonucleotides, cholesterol-lowering agents, dyslipidemia, HDL-modifying agents, microsomal triglyceride transfer protein inhibitors, peroxisome proliferator-activated receptor agonists, squalene synthase inhibitors, thyroid hormone receptor agonists, atherosclerotic cardiovascular disease, LDL- cholesterol levels
Current Medicinal Chemistry
Title: Emerging Targets for the Treatment of Dyslipidemia
Volume: 18 Issue: 6
Author(s): A. Tavridou, G. Ragia and V. G. Manolopoulos
Affiliation:
Keywords: Antisense oligonucleotides, cholesterol-lowering agents, dyslipidemia, HDL-modifying agents, microsomal triglyceride transfer protein inhibitors, peroxisome proliferator-activated receptor agonists, squalene synthase inhibitors, thyroid hormone receptor agonists, atherosclerotic cardiovascular disease, LDL- cholesterol levels
Abstract: Dyslipidemia is one of the main risk factors leading to atherosclerotic cardiovascular disease (CVD). According to recent treatment guidelines, subjects at substantial risk of CVD should meet more aggressive targets for low-density lipoprotein(LDL)- cholesterol levels. Treatment with statins fails to protect a significant percentage of patients from cardiovascular events despite efficient cholesterol-lowering. Moreover, clinical and epidemiologic data highlight the need of therapies to reduce the residual cardiovascular risk associated with low high-density lipoprotein(HDL)-cholesterol and elevated triglyceride levels. There are several novel agents undergoing preclinical or clinical development for the treatment of dyslipidemia. Squalene synthase inhibitors, antisense oligonucleotides targeting the production of apolipoprotein(apo)B-100, inhibitors of proprotein convertase subtilisin/kexin type 9, microsomal triglyceride transfer protein inhibitors, peroxisome proliferator-activated receptor agonists, and thyroid hormone receptor agonists are some of the alternative approaches for lipid-lowering. Moreover, HDL-targeted therapies such as the cholesteryl ester transfer protein inhibitors, HDLderived proteins, and mimetic peptides/lipids can increase HDL-cholesterol levels or improve the antiatherosclerotic properties of HDL. In conclusion, the emergence of agents that act in monotherapy or in combination with available lipid-modifying drugs may allow more effective management of dyslipidemia and, consequently, reduce the burden of CVD.
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Cite this article as:
Tavridou A., Ragia G. and G. Manolopoulos V., Emerging Targets for the Treatment of Dyslipidemia, Current Medicinal Chemistry 2011; 18 (6) . https://dx.doi.org/10.2174/092986711794927757
DOI https://dx.doi.org/10.2174/092986711794927757 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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