A High Throughput Biochemical Fluorometric Method For Measuring HDL Redox Activity

Tech ID: 29902 / UC Case 2014-425-0

Summary

UCLA researchers in the Department of Medicine have developed a method of screening for the functional properties of high-density lipoprotein (HDL) in the blood that may serve as a more accurate risk indicator of cardiovascular disease.

Background

Cardiovascular disease remains the number one cause of death for both men and women in the United States. According to a 2011 study by the Center for Disease Control, approximately 600,000 people die of heart disease in the United States every year, which is 1 in every 4 deaths[i]. HDLs and cardiovascular disease show an inverse correlation. However, growing evidence suggests that higher HDL levels are not always beneficial since HDL can become dysfunctional. Current methods of HDL testing only indicate the overall levels in the blood and say nothing about their size, density, composition, and functionality. All of these properties are associated with atherosclerosis, and the ability to measure them could become a great tool for diagnosing cardiovascular risk.

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[i] KD Kochanek, JQ Xu, SL Murphy, AM Miniño, HC Kung. Deaths: final data for 2009. National vital statistics reports. 2011 60(3)

Innovation

Dr. Theodore Kelesidis, Dr Srinu Reddy and Dr. Otto Yang have invented a method of measuring the functionality of HDLs by measuring their redox activity using the Amplex Red fluorochrome. This reproducible assay has a 96 well format, making it inexpensive, rapid, and suitable for high throughput screening applications. This invention can be used both in cardiovascular disease research to better understand the relationship between HDL redox activity and atherosclerosis, and in clinical settings as a tool for measuring cardiovascular risk in patients. This technology has the additional potential to be used in AIDS research, as there are also studies that correlate dysfunctional HDL with HIV[ii].

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[ii] Theodoros Kelesidis, Otto O. Yang, Judith S. Currier, Kaveh Navab, Alan M. Fogelman, and Mohamad Navab. HIV-1 infected patients with suppressed plasma viremia on treatment have pro-inflammatory HDL. Lipids in Health and Disease. 2011 10:35

Applications

  • Clinical cardiovascular disease diagnostic tool
  • Research cardiovascular disease diagnostic tool
  • HIV research
  • Research on diseases with systemic inflammation and oxidative stress (e.g. autoimmune diseases)

Advantages

  • More accurate indicator of cardiovascular risk
  • Inexpensive
  • Rapid
  • Scalable/high-throughput

State Of Development

  • The assay has been fully developed and tested, with current work involving testing multiple patient populations and using the assay to study HDL function.

Patent Status

Country Type Number Dated Case
United States Of America Published Application 20170059595 03/02/2017 2014-425
 

Related Materials

  • Theodoros Kelesidis, Judith S. Currier, Diana Huynh, David Meriwether, Christina Charles-Schoeman, Srinivasa T. Reddy, Alan M. Fogelman, Mohamad Navab, and Otto O. Yang A biochemical fluorometric method for assessing the oxidative properties of HDL. Journal of Lipid Research. 2011 52:(12) 2341-2351.
  • Kelesidis T, Reddy ST, Huynh D, Meriwether D, Fogelman AM, Navab M, Yang OO: Effects of Lipid-Probe Interactions in Biochemical Fluorometric Methods that Assess HDL Redox Activity. Lipids Health Dis. 2012; 11:87.
  • Roberts CK, Katiraie M, Croymans DM, Yang OO, Kelesidis T. Untrained Young Men Have Dysfunctional HDL Compared to Strength Trained Men Irrespective of Overweight/Obesity Status J Appl Physiol (1985). 2013; 115:1043-1049.
  • Kelesidis T, Roberts CK, Huynh D, Martínez-Maza O, Currier JS, Reddy ST, Yang OO. A High Throughput Biochemical Fluorometric Method for Measuring Lipid Peroxidation in HDL. PLoS One. 2014 Nov 4;9(11):e111716.
  • Zanni MV, Kelesidis T, Fitzgerald ML, Lo J, Abbara S, Wai B, Marmarelis E, Hernandez NJ, Yang OO, Currier JS, Grinspoon SK. HDL redox activity is increased in HIV-infected men in association with macrophage activation and noncalcified coronary atherosclerotic plaque. Antivir Ther. 2014;19(8):805-11.
  • Kelesidis T, Jackson N, McComsey GA, Wang X, Elashoff D, Dube MP, Brown TT, Yang OO, Stein JH, Currier JS. Oxidized lipoproteins are associated with markers of inflammation and immune activation in HIV-1 infection. AIDS. 2016 Nov 13;30(17):2625-2633.
  • Weight loss surgery in adolescents corrects high-density lipoprotein subspecies and their function. Davidson WS, Inge TH, Sexmith H, Heink A, Elder D, Hui DY, Melchior JT, Kelesidis T, Shah AS. Int J Obes (Lond). 2017 Jan;41(1):83-89.
  • Kelesidis T, Tran TT, Brown TT, Moser C, Ribaudo HJ, Dube MP, Yang OO, McComsey GA, Stein JH, Currier JS. Changes in plasma levels of oxidized lipoproteins and lipoprotein subfractions with atazanavir-, raltegravir-, darunavir-based initial antiviral therapy and associations with common carotid artery intima-media thickness: ACTG 5260s. Antivir Ther. 2017;22(2):113-126.
  • Kelesidis T, Oda MN, Borja MS, Yee Y, Ng KF, Huynh D, Elashoff D, Currier JS. Predictors of impaired HDL function in HIV-1 infected compared to uninfected individuals. J Acquir Immune Defic Syndr. 2017 Jul 1;75(3):354-363.
  • Sen Roy S, Nguyen HCX, Angelovich TA, Hearps AC, Diana H, Jaworowski A, Kelesidis T. Cell-free biochemical fluorometric enzymatic assay for high-throughput measurement of lipid peroxidation in High Density Lipoprotein. J Vis Exp. 2017 Oct 12;(128).
  • Angelovich TA, Hearps AC, Oda MN, Borja MS, Huynh D, Homann S, Jaworowski A, Kelesidis T. Dysfunctional high-density lipoprotein from HIV+ individuals promotes monocyte-derived foam cell formation in vitro. AIDS. 2017 Nov 13;31(17):2331-2336.
  • Kelesidis T, Kendall MA, Danoff A, Aberg JA, Currier JS, Schmidt AM. Soluble levels of receptor for advanced glycation endproducts and dysfunctional high-density lipoprotein in persons infected with human immunodeficiency virus: ACTG NWCS332. Medicine (Baltimore). 2018 Jun;97(22):e10955. PMID: 29851842.

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Inventors

  • Kelesidis, Theodoros

Other Information

Keywords

HDL, high-density lipoprotein, cardiovascular disease, CVD, high throughput screening, HTS, Amplex Red, redox, assay, fluorochrome, atherosclerosis, inflammation, oxidative stress, HIV, AIDS

Categorized As