Are HDL Enzyme Activities Better Indices of Cardio-Metabolic Risk than HDL-C Levels?


Affiliations

  • St. John’s Research Institute, Division of Nutrition, Bangalore, Karnataka, India
  • St. John's Medical college, Department of Biochemistry, Bangalore, Karnataka, India
  • St. Johns Research Institute, Division of Nutrition, Bangalore, Karnataka, India

Abstract

Metabolic Syndrome (MS) is a combination of physiological factors that result in increased risk for developing Cardio Vascular Diseases (CVD). One factor that has traditionally been accepted as being athero-protective is High Density Lipoprotein (HDL). However increasing reports suggest that plasma levels of HDL-C do not reflect its functionality, which is mainly attributed to its cargo of antioxidant enzymes. The study was aimed at assessing key HDL-associated enzymes as potentially better biomarkers in evaluating risk of MS and thus CVD than merely HDL-C levels in an urban South Indian population. The study consisted of patients with MS (n=41) and age matched controls (n=65). Anthropometry, routine blood biochemistry and HDL associated enzyme activities were measured. Of the HDL enzymes, paraoxonase-1 (PON-1) activity was seen to be lower whereas Lecithin Cholesterol Acyl Transferase (LCAT) was higher in subjects with MS (p<0.01). Multiple logistic regression showed that low PON-1 activity and high LCAT activity had an increased AOR for MS (RR=3.8, 95% CI-1.1, 13.3, p=0.035, and RR=17.5, 95% CI-3.9, 77.5, p<0.001 respectively), independent of HDL-C levels. This study demonstrates the prevalence of impaired function of HDL enzymes in patients with MS, which might promote inflammation, oxidative stress and atherogenesis. It also suggests that estimating the activities of key HDL enzymes such as PON-1 and LCAT could improve the accuracy of MS and CVD risk prediction than mere measurement of HDL-C levels.

Keywords

CVD, HDL-C, inflammation, LCAT, metabolic syndrome, PON-1

Subject Discipline

Biochemistry; lipids; lipoproteins

Full Text:

References

Wasir, J.S. and Misra, A. The metabolic syndrome in Asian Indians: Impact of nutritional and socio-economic transition in India. Metab. Syndr. Relat. Disord., 2004, 2, 14–23.

Joshi, S.R., Anjana, R.M., Deepa, M., Pradeepa, R., Bhansali, A. Dhandania, V.K. et al., Prevalence of dyslipidemia in urban and rural India: the ICMR-INDIAB study. PLoS One 2014, doi:10.1371/journal.pone.0096808.

Farbstein, D. and Levy, A.P. HDL dysfunction in diabetes: causes and possible treatments. Expert Rev. Cardiovasc. Ther., 2012, 10, 353–361.

Haas, M.J. and Mooradian, A.D. Inflammation, high-density lipoprotein and cardiovascular dysfunction. Curr. Opin. Infect. Dis., 2011, 24, 265–272.

Dodani, S., Kaur, R., Reddy, S., Reed, G.L., Navab, M. and George, V. Can dysfunctional HDL explain high coronary artery disease risk in South Asians? Int. J. Cardiol., 2008, 129, 125–132.

Dodani, S. Excess coronary artery disease risk in South Asian immigrants: Can dysfunctional high-density lipoprotein explain increased risk? Vasc. Health Risk Manag., 2008, 4, 953–961.

Sini, S. and Jayakumari, N. Functionally defective high density lipoprotein is pro-oxidant: a deviation from normal atheroprotective character. Int. J. Fd. Sci. Nutr., 2013, 2, 92–101.

Navab. M., Hama, S.Y., Hough, G.P., Subbanagounder, G., Reddy, S.T. and Fogelman, A.M. A cell-free assay for detecting HDL that is dysfunctional in preventing the formation of or inactivating oxidized phospholipids. J. Lipid Res., 2001, 42, 1308–1317.

Burlina, A., Michielin, E. and Galzigna, L. Characteristics and behavior of arylesterase in human serum and liver. Eur. J. Clin. Invest., 1977, 7, 17–20.

Krueger, A.J., Yang, J.J., Roy, T.A., Robbins, D.J. and Mackerer, C.R. An automated myeloperoxidase assay. Clini. Chem., 1990, 36, 158.

Ramachandran, A., Ma, R.C. and Snehalatha, C. Diabetes in Asia. Lancet., 2010, 30, 408-418. doi: 10.1016/S0140-6736(09)60937-5.

Srikanthan, K., Feyh, A., Visweshwar, H., Shapiro, J.I. and Sodhi, K. Systematic review of metabolic syndrome biomarkers: A panel for early detection, management and risk stratification in the West Virginian population. Int. J. Med. Sci., 2016, 13, 25-38. doi: 10.7150/ijms.13800.

Paneni, F., Cosentino, F., Marrara, F., Palano, F., Capretti, G., Gregori, M. The clinical relevance of dysfunctional HDL in patients with coronary artery disease: A 3-year follow-up study. Int. J. Cardiol., 2012, 158–160.

Baron, A.A. and Baron, S.B. High levels of HDL cholesterol do not predict protection from cardiovascular disease in women. Prev. Cardiol., 2007, 10, 125–127.

Mackness, M.I., Arrol, S., Abbott, C. and Durrington, P.N. Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase. Atherosclerosis, 1993, 104, 129–135.

Mackness, M.I., Arrol, S. and Durrington, P.N. Paraoxonase prevents accumulation of lipoperoxides in low-density lipoprotein. FEBS Lett., 1991, 286, 152–154.

Heinecke, J.W. and Lusis, A.J. Paraoxonase-gene polymorphisms associated with coronary heart disease: support for the oxidative damage hypothesis? Am. J. Hum. Genet., 1998, 62, 20–24.

Mastorikou, M., Mackness, M. and Mackness, B. Defective metabolism of oxidized phospholipid by HDL from people with type 2 diabetes. Diabetes, 2006, 55, 3099-3103.

Baynes, J.W. Role of oxidative stress in development of complications in diabetes. Diabetes, 1991, 40, 405–412.

Flekac, M., Skrha, J., Zidkova, K., Lacinová, Z. and Hilgertova, J. Paraoxonase 1 gene polymorphisms and enzyme activities in diabetes mellitus. Physiol. Res., 2008, 57, 717–726.

Mogarekar, M.R., Dhabe, M.G. and Gujrathi, C.C. A study of paraoxonase1 (PON1) activities, HDL cholesterol and its association with vascular complication in type 2 diabetes mellitus. Int. J. Diab. Dev. Countries, 2016, 1–6.

Amine, K., Atouk, A., Moussamih, S., Saile, R., Mikou, A. and Kettani, A. Paraoxonase-1 (PON1) activity in patients with coronary artery diseases and in diabetic patients. Ann. Biol. Clin., 2011, 69, 671–677.

Dullaart, R.P., Perton, F., van der Klauw, M.M., Hillege, H.L., Sluiter, W.J. et al., High plasma lecithin: cholesterol acyltransferase activity does not predict low incidence of cardiovascular events: possible attenuation of cardio protection associated with high HDL cholesterol. Atherosclerosis, 2010, 208, 537–542.

Holleboom, A.G., Kuivenhoven, J.A., Vergeer, M., Hovingh, G.K., van Miert, J.N., Wareham, N.J. et al. Plasma levels of lecithin: cholesterol acyltransferase and risk of future coronary artery disease in apparently healthy men and women: A prospective case-control analysis nested in the EPIC-Norfolk population study. J. Lipid Res., 2010, 51, 416–421.

McPherson, P.A., Young, I.S. and McEneny, J. A dual role for lecithin: cholesterol acyltransferase (EC 2.3. 1.43) in lipoprotein oxidation. Free Radic. Biol. Med., 2007, 43, 1484–1493.

Gruppen, E.G., Connelly, M.A., Otvos, J.D., Bakker, S.J. and Dullaart, R.P. A novel protein glycan biomarker and LCAT activity in metabolic syndrome. Eur. J. Clin. Invest., 2015, 45, 850–859. doi: 10.1111/eci.12481.

Ng, D.S. Lecithin cholesterol acyltransferase deficiency protects from diet-induced insulin resistance and obesity—novel insights from mouse models. Vitam. Horm., 2013, 91, 259-270. doi: 10.1016/B978-0-12-407766-9.

Esser, N., Legrand-Poels, S., Piette, J., Scheen, A.J. and Paquot, N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res. Clin. Pract., 2014, 105, 141–150.

Schindhelm, R.K., van der Zwan, L.P., Teerlink, T. and Scheffer, P.G. Myeloperoxidase: A useful biomarker for cardiovascular disease risk stratification? Clin. Chem., 2009, 55, 1462–1470.

Morgantini, C., Natali, A., Boldrini, B., Imaizumi, S., Navab, M., Fogelman, A.M., et al., Anti-inflammatory and antioxidant properties of HDLs are impaired in type 2 diabetes. Diabetes, 2011, 60, 2617–2623.


Refbacks

  • There are currently no refbacks.