Journal
CELLS
Volume 11, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/cells11030313
Keywords
hypercholesterolemia; PXR; SREBP2; PCSK9
Categories
Funding
- Academy of Finland [286743, 323706]
- Novo Nordisk Foundation [NNF14OC0010653, NNF15OC0015846]
- Finnish Medical Foundation
- Finnish Foundation for Cardiovascular Research
- Northern Finland Health Care Support Foundation
- Diabetes Research Foundation
- European Union's Horizon 2020 research and innovation programme [825762]
- Academy of Finland (AKA) [323706, 286743, 323706, 286743] Funding Source: Academy of Finland (AKA)
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Atherosclerosis is a global health concern with high total and LDL cholesterol as the main risk factors. Understanding the factors influencing an individual's cholesterol levels during the formation of arteriosclerotic plaques is crucial. Activation of pregnane X receptor (PXR) has been shown to induce hypercholesterolemia and may play a role in drug-induced high cholesterol levels.
Atherosclerosis is a major global health concern. The central modifiable risk factors and causative agents of the disease are high total and low-density lipoprotein (LDL) cholesterol. To reduce morbidity and mortality, a thorough understanding of the factors that influence an individual's cholesterol status during the decades when the arteria-narrowing arteriosclerotic plaques are forming is critical. Several drugs are known to increase cholesterol levels; however, the mechanisms are poorly understood. Activation of pregnane X receptor (PXR), the major regulator of drug metabolism and molecular mediator of clinically significant drug-drug interactions, has been shown to induce hypercholesterolemia. As a major sensor of the chemical environment, PXR may in part mediate hypercholesterolemic effects of drug treatment. This review compiles the current knowledge of PXR in cholesterol homeostasis and discusses the role of PXR in drug-induced hypercholesterolemia.
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