Background Low testosterone levels are associated with an increased incidence of cardiovascular (CV) events, but the underlying biochemical mechanisms are not fully understood. The clinical condition of hypogonadism offers a unique model to unravel the possible role of lipoprotein-associated abnormalities in CV risk. In particular, the assessment of the functional capacities of high-density lipoproteins (HDL) may provide novel insights besides traditional risk factors. To determine whether reduced testosterone levels correlate with lipoprotein function, HDL cholesterol efflux capacity (CEC) and serum cholesterol loading capacity (CLC) were evaluated in a series of genetic and idiopathic hypogonadal patients and control subjects. Methods and Results Primary and secondary hypogonadal patients presented with lower HDL ATP-binding cassette transporter A1 (ABCA1)-, ATP binding cassette transporter G1 (ABCG1) - and aqueous diffusion-mediated CEC (-19.6%, -40.9% and -12.9%, respectively), with a 16.2% decrement of total CEC. In the whole series, positive correlations between testosterone levels and both total HDL CEC (r2= 0.359, p= 0.0001) and ABCG1 HDL CEC (r2= 0.367, p= 0.0001) were observed. Conversely, serum CLC was markedly raised (+43%) in hypogonadals, being increased, to a higher extent, in primary vs secondary hypogonadism (18.45 ± 2.78 vs 15.15 ± 2.10 µg cholesterol/mg protein) and inversely correlated with testosterone levels (r2= 0.270, p= 0.001). HDL-C concentrations did not correlate with either testosterone levels, HDL CEC (total, ABCG1 and ABCA1) or serum CLC. Conclusion(s) In hypogonadal patients pro-atherogenic lipoprotein-associated changes are associated with lower cholesterol efflux and increased influx, thus offering an explanation for a potentially increased CV risk.

High density lipoprotein function is reduced in patients affected by genetic or idiopathic hypogonadism / M.P. Adorni, F. Zimetti, B. Cangiano, V. Vezzoli, F. Bernini, D. Caruso, A. Corsini, C.R. Sirtori, A. Cariboni, M. Bonomi, M. Ruscica. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. - ISSN 0021-972X. - 104:8(2019 Jun 19), pp. 3097-3107.

High density lipoprotein function is reduced in patients affected by genetic or idiopathic hypogonadism

B. Cangiano
Methodology
;
V. Vezzoli
Methodology
;
D. Caruso
Methodology
;
A. Corsini
Supervision
;
A. Cariboni
Writing – Review & Editing
;
M. Bonomi
Penultimo
Writing – Review & Editing
;
M. Ruscica
Ultimo
Writing – Original Draft Preparation
2019

Abstract

Background Low testosterone levels are associated with an increased incidence of cardiovascular (CV) events, but the underlying biochemical mechanisms are not fully understood. The clinical condition of hypogonadism offers a unique model to unravel the possible role of lipoprotein-associated abnormalities in CV risk. In particular, the assessment of the functional capacities of high-density lipoproteins (HDL) may provide novel insights besides traditional risk factors. To determine whether reduced testosterone levels correlate with lipoprotein function, HDL cholesterol efflux capacity (CEC) and serum cholesterol loading capacity (CLC) were evaluated in a series of genetic and idiopathic hypogonadal patients and control subjects. Methods and Results Primary and secondary hypogonadal patients presented with lower HDL ATP-binding cassette transporter A1 (ABCA1)-, ATP binding cassette transporter G1 (ABCG1) - and aqueous diffusion-mediated CEC (-19.6%, -40.9% and -12.9%, respectively), with a 16.2% decrement of total CEC. In the whole series, positive correlations between testosterone levels and both total HDL CEC (r2= 0.359, p= 0.0001) and ABCG1 HDL CEC (r2= 0.367, p= 0.0001) were observed. Conversely, serum CLC was markedly raised (+43%) in hypogonadals, being increased, to a higher extent, in primary vs secondary hypogonadism (18.45 ± 2.78 vs 15.15 ± 2.10 µg cholesterol/mg protein) and inversely correlated with testosterone levels (r2= 0.270, p= 0.001). HDL-C concentrations did not correlate with either testosterone levels, HDL CEC (total, ABCG1 and ABCA1) or serum CLC. Conclusion(s) In hypogonadal patients pro-atherogenic lipoprotein-associated changes are associated with lower cholesterol efflux and increased influx, thus offering an explanation for a potentially increased CV risk.
Settore MED/04 - Patologia Generale
Settore MED/13 - Endocrinologia
Settore BIO/14 - Farmacologia
Settore BIO/10 - Biochimica
Settore BIO/13 - Biologia Applicata
   Aged-related obesity and chronic immunoinflammation: understanding the relevance and pathophysiology of lactate
   FONDAZIONE CARIPLO
   2015-0552
19-giu-2019
5-mar-2019
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/630525
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