Circulating Complex of Lipoprotein(a) and Proprotein Convertase Subtilisin/Kexin Type 9 in the Serum Measured by ELISA
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Bulletin of Experimental Biology and Medicine, Vol. 169, No. 5, September, 2020 BIOPHYSICS AND BIOCHEMISTRY
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Circulating Complex of Lipoprotein(a) and Proprotein Convertase Subtilisin/Kexin Type 9 in the Serum Measured by ELISA O. A. Razova, O. I. Afanas’eva, M. G. Egiazaryan, E. E. Sherstyuk, E. A. Klesareva, and S. N. Pokrovskii
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 169, No. 5, pp. 568-572, May, 2020 Original article submitted December 6, 2019 The presence of a complex of lipoprotein(a) and proprotein convertase subtilisin/kexin type 9 (PCSK9) in the blood of healthy volunteers and patients with cardiovascular diseases was analyzed by ELISA. The levels of the complex varied in a wide range and did not depend on the concentrations of Lp(a) and PCSK9. Moreover, the complex was found not only in patients with cardiovascular diseases, but also in healthy volunteers, which can indicate physiological role of lipoprotein(a) as PCSK9 transporter. Key Words: PCSK9; lipoprotein(a); complex; enzyme-linked ELISA Increased concentration of lipoprotein(a) (Lp(a)), or hyperlipoproteinemia(a), is an independent genetic risk factor of atherosclerosis in different vascular basins and is associated with cardiovascular complications. Recent studies have demonstrated that increased level of proprotein convertase subtilisin/kexin type 9 (PCSK9) is a marker of atherosclerosis in coronary and peripheral arteries in patients with heterozygous familial hypercholesterolemia and correlates with the severity of this disease [5]. Lp(a) is a complex supramolecular structure consisting of apoB-100-containing particle, similar to LDL, and highly glycosylated and extremely polymorphic apoprotein(a), unique to the lipoprotein(a) family. The plasma level of Lp(a) is genetically determined and resistant to current lipidlowering agents. Therapeutic monoclonal antibodies that block PCSK9 activity and prevent degradation of LDL receptor opened a new era in the treatment of severe lipid metabolism disorders [1,13]. The ability of PCSK9 inhibitors to decrease the concentration of Lp(a) by 30% was surprising, because LDL-receptor practically does not participate in Lp(a) catabolism [9]. National Medical Research Center of Cardiology, Ministry of Health of the Russian Federation, Moscow, Russia. Address for correspondence: [email protected]. O. A. Razova
Despite conducted studies, this phenomenon remains unclear. A possible mechanism can be the formation of circulating immune complex between the therapeutic anti-PCSK9 antibodies and PCSK9 bound to Lp(a) [Lp(a)—PCSK9] followed by eliminated of the latter from the bloodstream. We have earlier shown that the concentration of Lp(a) correlates with the level of PCSK9 circulating in plasma of statin-naïve patients with newly diagnosed hyperlipidemia [2]. Polymorphism of apoprotein(a) is the key factor in the interaction between these parameters [2]. As the mechanisms of high atherogenicity of Lp(a) and its physiological role are still unclear, we hypothesized that Lp(a) c
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