Hormone replacement therapy increases levels of antibodies against heat shock protein 65 and certain species of oxidized low density lipoprotein

Abstract

Hormone replacement therapy (HRT) reduces cardiovascular risks, although the initiation of therapy may be associated with transient adverse ischemic and thrombotic events. Antibodies against heat shock protein (Hsp) and oxidized low density lipoprotein (LDL) have been found in atherosclerotic lesions and plasma of patients with coronary artery disease and may play an important role in the pathogenesis of atherosclerosis. The aim of the present study was to assess the effects of HRT on the immune response by measuring plasma levels of antibodies against Hsp 65 and LDL with a low and high degree of copper-mediated oxidative modification of 20 postmenopausal women before and 90 days after receiving orally 0.625 mg equine conjugate estrogen plus 2.5 mg medroxyprogesterone acetate per day. HRT significantly increased antibodies against Hsp 65 (0.316 ± 0.03 vs 0.558 ± 0.11) and against LDL with a low degree of oxidative modification (0.100 ± 0.01 vs 0.217 ± 0.02) (P<0.05 and P<0.001, respectively, ANOVA). The hormone-mediated immune response may trigger an inflammatory response within the vessel wall and potentially increase plaque burden. Whether or not this immune response is temporary or sustained and deleterious requires further investigation.

Autoantibodies against oxidized low-density lipoprotein and lipid profile in patients with chronic periaortitis: case–control study

“…The risk of a primary immune response increases with the formation of aOxLDL antibodies. Postmenopausal hormone replacement therapy may (33) or may not reduce aOxLDL levels (34,36). However, none of our female patients or controls used hormonal replacement therapy.…”

Soy protein containing isoflavones favorably influences macrophage lipoprotein metabolism but not the development of atherosclerosis in CETP transgenic mice

“…Nonetheless, the results remain controversial in humans; Heikkinen et al (38) did not find differences in ox-LDL antibodies titers in postmenopausal women after one year on hormonal replacement, whereas Uint et al (39) described increased anti-ox-LDL titers after 90 d on this treatment. In this regard, Wen et al (40) and Santanam et al (41) showed that, except for plasma concentrations over 7343 pmol/L, estrogens at physiological concentrations (499 to 4,993 pg/mL) do not protect LDL particles against oxidation.…”

Selective Estrogen Receptor Modulators

“…Only supraphysiological doses have demonstrated this effect in the laboratory (Hermenegildo et al 2001;Santanam et al 1998). Some indirect evidence favoring protection, such as the reduction of antibodies to oxidized LDL, has been proposed (Hoogerbrugge et al 1998), but, again, there is no general consensus on the subject (Uint et al 2003;Heikkinen et al 1998). More recent research has found that estrogens reduce the production of F 2α -isoprostanes, a product of a nonenzymatic, free radical catalyzed peroxidation of arachidonic acid (Liu et al 1998) that has been recognized as a stable, good biomarker of in vivo oxidative stress (de Zwart et al 1999;Pratico 1999).…”