Original Contributions |
From the Departments of Internal Medicine (V.M., P.F., V.L., P.N.) and Cardiovascular Surgery (F.T., P.R., L.K.v.S.), the Central Laboratory of Clinical Chemistry (M.V., M.M.), and Medical Policlinic (R.D.), CHUV University Hospital, Lausanne, Switzerland; and the Department of Medicine, Northwest Lipid Research Laboratories, University of Washington, Seattle (S.M.M.).
Correspondence to Vincent Mooser, MD, Department of Internal Medicine, BH 19/135, CH-1011 CHUV Lausanne, Switzerland. E-mail vincent.mooser{at}hola.hospvd.ch
AbstractFragments of apolipoprotein(a) [apo(a)], the distinctive glycoprotein of lipoprotein(a) [Lp(a)], are present in human plasma and urine and have been implicated in the development of atherosclerosis. The mechanism responsible for the generation of apo(a) fragments in vivo is poorly understood. In this study, we examined the plasma levels of Lp(a) and apo(a) fragments [or free apo(a)] and urinary apo(a) in 15 subjects who underwent cardiac surgery necessitating cardiopulmonary bypass. We also measured the plasma concentration and activity of polymorphonuclear elastase, an Lp(a)-cleaving enzyme in vitro, and plasma levels of C-reactive protein. Despite a marked activation of polymorphonuclear cells and a pronounced inflammatory response, as documented by an 8-fold and a 35-fold increase in plasma levels of polymorphonuclear elastase and C-reactive protein, respectively, the proportion of plasma free apo(a) to Lp(a) and urinary excretion of apo(a) remained unchanged over a 7-day period after surgery, and polymorphonuclear elastase activity remained undetectable in plasma. No fragmentation of apo(a) was observed ex vivo in plasma samples collected before and after surgery. These data indicate that in this model, apo(a) is not fragmented in plasma and are consistent with the hypothesis that apo(a) fragments result from a constitutively active tissue mechanism that is not modified by cardiac surgery with cardiopulmonary bypass.
Key Words: apolipoprotein(a) atherosclerosis elastase heparin lipoprotein(a)
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