Review Dysfunctional HDL: A novel important diagnostic and therapeutic target in cardiovascular disease? Aneta Otocka-Kmiecik a , Dimitri P. Mikhailidis b , Stephen J. Nicholls c , Michael Davidson d , Jacek Rysz e , Maciej Banach a,⇑ a Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland b Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, UK c Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA d University of Chicago, Pritzker School of Medicine, Chicago, USA e Department of Nephrology, Hypertension and Family Medicine, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland article info Article history: Received 17 February 2012 Received in revised form 22 March 2012 Accepted 23 March 2012 Available online 15 May 2012 Keywords: Dyslipidemia High density cholesterol Inflammation Lipids Therapy abstract High density lipoprotein (HDL) has many properties, which contribute to its atheroprotective role. How- ever, some recent clinical trials have identified subjects with the progression of atherosclerosis despite normal levels of HDL cholesterol. This raises the question if all subfractions of HDL have the same prop- erties. Moreover, recent investigations have shown that both acute and chronic inflammation may lead to structural and functional changes of HDL, which render the particles proinflammatory. Although thera- peutic agents that increase HDL levels are now quite well established it is not clear whether they influ- ence HDL quality. We review the current state of knowledge on the properties of HDL and factors/therapeutic agents which may restrain the transformation of normal HDL into dysfunctional HDL. Ó 2012 Elsevier Ltd. All rights reserved. Contents 1. Introduction ......................................................................................................... 315 2. Search strategy ....................................................................................................... 315 3. HDL subfractions ..................................................................................................... 315 4. Anti-atherosclerotic role of HDL ......................................................................................... 315 4.1. Cholesterol efflux capacity ........................................................................................ 315 4.2. Anti-inflammatory role of HDL..................................................................................... 316 4.3. Antithrombotic activity of HDL .................................................................................... 316 4.4. Profibrinolytic function of HDL..................................................................................... 316 4.5. Antioxidant properties of HDL ..................................................................................... 316 5. Modification of HDL in pathological states ................................................................................. 316 6. HDL functionality determination......................................................................................... 317 7. Treatment options and dysfunctional HDL ................................................................................. 318 7.1. Reconstituted high-density lipoprotein (rHDL) ........................................................................ 318 7.2. Therapeutic effect of Apo A-I ...................................................................................... 318 7.3. Apolipoprotein – mimetic peptides ................................................................................. 318 7.4. Targeting myeloperoxidase (MPO) .................................................................................. 319 7.5. Iron (III) corrole catalytic antioxidant (1-Fe) .......................................................................... 319 7.6. Cholesteryl ester transfer protein (CETP) inhibitors .................................................................... 319 7.7. Nicotinic acid (niacin) ............................................................................................ 320 0163-7827/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.plipres.2012.03.003 ⇑ Corresponding author. Address: Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz, Zeromskiego 113, 90-549 Lodz, Poland. Tel.: +48 42 639 37 71; fax: +48 42 639 37 82. E-mail address: maciejbanach@aol.co.uk (M. Banach). Progress in Lipid Research 51 (2012) 314–324 Contents lists available at SciVerse ScienceDirect Progress in Lipid Research journal homepage: www.elsevier.com/locate/plipres