Abstract
Achilles tendon xanthomas are associated with increased cardiovascular risk in patients with familial hypercholesterolemia (FH). Oxidized low density lipoprotein (OxLDL), the antibodies against OxLDL, and the LDL-associated phospholipase A(2) (Lp-PLA(2)) may play important roles in atherogenesis. We investigated the possible association between plasma levels of OxLDL, Lp-PLA(2) activity, and autoantibody titers against various types of mildly OxLDL with Achilles tendon thickness (ATT). ATT was determined by sonography in 80 unrelated heterozygous FH patients. Three different types of mildly OxLDL were prepared: OxLDL(L), OxLDL(P), and OxLDL(D), at the end of the lag, propagation, and decomposition phases of oxidation, respectively. Similar types of OxLDL were also prepared after inactivation of the LDL-associated Lp-PLA(2). These types were denoted OxLDL(-)(L), OxLDL(-)(P), and OxLDL(-)(D). FH patients exhibited significantly higher plasma OxLDL levels and serum IgG titers against OxLDL(P) and OxLDL(D) compared with 40 normolipidemic apparently healthy controls. ATT values were positively correlated with autoantibody titers against OxLDL(P) and OxLDL(D); however, in multiple regression analysis, ATT was independently associated only with the autoantibody titers against OxLDL(D). We conclude that the IgG autoantibody titers against OxLDL(D) but not OxLDL or Lp-PLA(2) may play an important role in the pathogenesis of Achilles tendon xanthomas in FH patients.
Highlights
Achilles tendon xanthomas are associated with increased cardiovascular risk in patients with familial hypercholesterolemia (FH)
This study shows for the first time that autoantibodies against mildly Oxidized low density lipoprotein (OxLDL) are increased in patients with heterozygous FH and, most importantly, that autoantibodies against OxLDLD are independently associated with Achilles tendon thickness (ATT)
The plasma levels of OxLDL or LDLassociated phospholipase A2 (Lp-PLA2) activity, increased significantly in FH patients compared with controls, are not correlated with ATT
Summary
Achilles tendon xanthomas are associated with increased cardiovascular risk in patients with familial hypercholesterolemia (FH). We investigated the possible association between plasma levels of OxLDL, Lp-PLA2 activity, and autoantibody titers against various types of mildly OxLDL with Achilles tendon thickness (ATT). We conclude that the IgG autoantibody titers against OxLDLD but not OxLDL or Lp-PLA2 may play an important role in the pathogenesis of Achilles tendon xanthomas in FH patients.—Tsouli, S. OxLDL is immunogenic, and its constituents OxPL, aldehydes, and lyso-PC play important roles in OxLDL antigenicity, participating in the formation of several epitopes [6, 7] These epitopes are recognized by specific autoantibodies, which are present in serum of healthy individuals as well as in various disease states, including atherosclerotic diseases (reviewed in 8). Because the extent of LDL oxidation and the LDL-associated Lp-PLA2 activity significantly influence the levels of OxPL, lyso-PC, and aldehydes during LDL oxidation [9], these factors could influence the types of epitopes formed on OxLDL and the specificity and the plasma. We recently showed that the extent of LDL oxidation and the activity of LDL-associated Lp-PLA2 significantly affect the antibody titers against OxLDL [10]
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