an inverse anticipated relationship of lppl2 and diabetes
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An Inverse Anticipated Relationship of Lppl2 and DiabetesTRANSCRIPT
European Journal of Internal Medicine 26 (2015) 72
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European Journal of Internal Medicine
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Letter to the Editor
An inverse-to-anticipated relationship ofLp-PLA2 activity in diabetes: Reflection of
underlying autoimmune activationKeywords:Autoimmune activationDiabetes mellitusLipoprotein-associated phospholipase A2 activity
Dear Editor,
The study by Mayer Jr. and associates [1] investigating the relation-ship between impaired glucose metabolism and lipoprotein-associatedphospholipase A2 activity (aLp-PLA2) contributes to current knowledge.In a cross-sectional analysis of 825 patients with stable coronary heartdisease (CHD) and/or stroke, they observed inverse relationships ofaLp-PLA2 with high fasting glycemia, glycated hemoglobin A1c andwith quartiles of LDLc/apoB ratio. Authors concluded that the presenceof diabetes was independently associated with lower likelihood of ele-vated aLp-PLA2 and postulated a redistribution of aLp-PLA2 from apoBto high-density lipoprotein particles to account for their observation.Previously, in a cross-sectional analysis of an elderly sample of about1000 Swedish subjects, aLp-PLA2 was found not to be independently re-lated to carotid atherosclerosis and to the amount of arterial stenosis [2].Authors considered that aLp-PLA2 levelsmay not constitute a good indi-cator of the activity within atherosclerotic lesions. We had documentedin a population-based sample (n = 736) that circulating Lp-PLA2 masswas independently associated with prevalent and incident CHD inmen, though being inversely associated only with diabetes in men,and only with metabolic syndrome (MetS) in women [3].
We propose a unified explanation to encompass these findings,namely, existence of a non-linear, U-shaped relationship between Lp-PLA2 and cardiometabolic risk, in a gender-modulated environment ofpro-inflammatory state. Several other proteins are considered to besubject to the same autoimmune mechanism [4], reviewed elsewhere[5]. Lp-PLA2mass, concentrated on plasma lipoprotein (a), amajor insti-gator of enhanced inflammation and autoimmune activation, is sensi-tive to enhanced pro-inflammatory state. The enzyme epitope thusmay become partly damaged, inducing aggregation and autoimmune
http://dx.doi.org/10.1016/j.ejim.2014.10.0100953-6205/© 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rig
complex formation with a protective protein (such as apolipoproteinA-I). It partly escapes immunoassay, resulting in apparently “reduced”mass (and/or activity), and further fails to exhibit anticipated relation-ship to inflammation markers or cardiometabolic risk [5]. Diabetesand the female sex aremainmodulators of this process. This notion clin-ically implicates the development of new preventive and therapeuticapproaches.
Conflict of interests
The authors declare that they have no conflict of interest regardingthis letter.
References
[1] Mayer Jr O, Seidlerová J, Filipovský J, Timoracká K, Bruthans J, Vaněk J, et al. Unexpectedinverse relationship between impaired glucose metabolism and lipoprotein-associatedphospholipase A2 activity in patients with stable vascular disease. Eur J Intern Med2014;25:556–60.
[2] Lind L, Simon T, Johansson L, Kotti S, Hansen T,Machecourt J, et al. Circulating levels ofsecretory- and lipoprotein-associated phospholipase A2 activities: relation to athero-sclerotic plaques and future all-cause mortality. Eur Heart J 2012;33:2946–54.
[3] Onat A, Hergenç G, Can G, Uğur M, Nartop F. Dual activity of serum lipoprotein-associated phospholipase A2 yielding positive and inverse associations with cardio-metabolic risk. Clin Chem Lab Med 2011;49:1349–57.
[4] Onat A, Can G, Ademoğlu E, Çelik E, Karagöz A, Örnek E. Coronary disease risk curve ofserum creatinine is linear in Turkish men, U-shaped in women. J Investig Med 2013;61:27–33.
[5] Onat A, Can G. Enhanced proinflammatory state and autoimmune activation: a break-through to understanding chronic diseases. Curr Pharm Des 2014;20:575–84.
Altan OnatDepartments of Cardiology, Cerrahpaşa Medical Faculty, Istanbul
University, Istanbul 34335, TurkeyCorresponding author. Tel.: +90 212 351 6217.E-mail address: [email protected] (A. Onat).
Tuğba AkbaşBagcilar Educ. Hospital, Istanbul 34335, Turkey
Hüsniye YükselDepartments of Cardiology, Cerrahpaşa Medical Faculty, Istanbul
University, Istanbul 34335, Turkey
2 October 2014
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