Therapeutic Approaches to the Regulation of Metabolism of High-Density Lipoprotein : Novel HDL-Directed Pharmacological Intervention and Exercise

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Author(s)

    • ZHANG Bo
    • Department of Biochemistry, Fukuoka University School of Medicine
    • KAWACHI Emi
    • Department of Cardiology, Fukuoka University School of Medicine
    • MIURA Shin-ichiro
    • The AIG Collaborative Research Institute of Cardiovascular Medicine, Fukuoka University School of Medicine
    • UEHARA Yoshinari
    • The AIG Collaborative Research Institute of Cardiovascular Medicine, Fukuoka University School of Medicine
    • MATSUNAGA Akira
    • The AIG Collaborative Research Institute of Cardiovascular Medicine, Fukuoka University School of Medicine
    • SAKU Keijiro
    • The AIG Collaborative Research Institute of Cardiovascular Medicine, Fukuoka University School of Medicine

Abstract

High-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles transport cholesterol in plasma and play an important role in cellular cholesterol homeostasis, which influences cell function. The risk of coronary artery disease (CAD) associated with high levels of LDL-cholesterol (LDL-C) can be reduced by treatment with statins, which reduce LDL-C levels by inhibiting cellular cholesterol synthesis. However, patients who are treated with high doses of statins, especially secondary CAD prevention, regardless of their resulting LDL-C levels, are still at high risk of CAD. Therefore, there has been growing interest in HDL-directed therapies. Inhibitors of cholesteryl ester transfer protein (CETP) substantially increase HDL-C levels (by 31–138%). However, it is still unclear whether or not CETP inhibitors can reduce the risk of CAD associated with low HDL-C levels, while reconstituted HDL or apolipoprotein A-I mimetic peptides increase the functionality of HDL. Low levels of HDL-C are often complicated with metabolic disorders, including hypertriglyceridemia, metabolic syndrome, and type 2 diabetes mellitus, and lifestyle changes are effective for correcting these conditions. Physical activity and exercise training increase HDL-C levels, especially HDL<sub>2</sub>-C levels, by multiple mechanisms. Therefore, although using HDL-directed therapies that increase HDL-C levels and/or improve the function of HDL is a reasonable approach for reducing the residual risk of CAD as a complement to LDL-C-lowering therapy, lifestyle modifications including exercise to improve metabolic disorders should be considered as the first option.  (<i>Circ J</i> 2013; <b>77:</b> 2651–2663)<br>

Journal

  • Circulation Journal

    Circulation Journal 77(11), 2651-2663, 2013-10-25

    The Japanese Circulation Society

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