The effect of transgender hormonal treatment on high density lipoprotein cholesterol efflux capacity

Velzen, Daan van; Adorni, Maria Pia; Zimetti, F.; Strazzella, Arianna; Şimşek, Suat; Sirtori, Cesare R.; Heijer, Martin den; Ruscica, Massimiliano

doi:10.1016/j.atherosclerosis.2021.03.008

Cited by 20 publications

(14 citation statements)

References 54 publications

(58 reference statements)

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“…High plasma levels of estrogen in murine models have also shown to increase de novo lipid clearance of VLDL and LDL, increase synthesis of HDL and alter the expression of lipoprotein modifiers (Villa et al, 2012;Della Torre et al, 2016). In contrast, a study in macrophages taken from trans-women undergoing sex hormone therapy showed that the total HDL efflux decreased by 10.8% and ATP-binding cassette transporter A1 (ABCA1)-mediated HDL efflux by 23.8%; this hormone-driven effect may therefore be tissue specific (van Velzen et al, 2021). In addition, a study has reported that male patients with primary and secondary hypogonadism (low testosterone) presented with lower ABCA1/G1, suggesting an association with reduced cholesterol efflux (Adorni et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Sex hormones drive changes in lipoprotein metabolism

et al. 2021

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Summary Women have a reduced cardiovascular disease (CVD) risk compared with men, which could be partially driven by sex hormones influencing lipid levels post puberty. The interrelationship between sex hormones and lipids was explored in pre-pubertal children, young post-pubertal cis-men/women, and transgender individuals on cross-sex-hormone treatment (trans-men/women) using serum metabolomics assessing 149 lipids. High-density lipoproteins (HDL, typically atheroprotective) were significantly increased and very-low- and low-density lipoproteins (typically atherogenic) were significantly decreased in post-pubertal cis-women compared with cis-men. These differences were not observed pre-puberty and were induced appropriately by cross-sex-hormone treatment in transgender individuals, supporting that sex hormones regulate lipid metabolism in vivo . Only atheroprotective apolipoprotein (Apo)A1 expressing lipoproteins (HDL) were differentially expressed between all hormonally unique comparisons. Thus, estradiol drives a typically atheroprotective lipid profile through upregulation of HDL/ApoA1, which could contribute to the sexual dimorphism observed in CVD risk post puberty. Together, this could inform sex-specific therapeutic strategies for CVD management.

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Section: Discussionmentioning

confidence: 99%

Sex hormones drive changes in lipoprotein metabolism

et al. 2021

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“…HDL’s capacity to promote cholesterol efflux (CEC) through the main pathways was evaluated in patients’ HDL fraction by a standardized and widely used radioisotopic cell-based technique [ 53 ]. For HDL fraction isolation, the apoB-containing lipoproteins were precipitated from whole serum with a solution of polyethylene glycol [ 54 ].…”

Section: Methodsmentioning

confidence: 99%

HDL Cholesterol Efflux and Serum Cholesterol Loading Capacity Alterations Associate to Macrophage Cholesterol Accumulation in FH Patients with Achilles Tendon Xanthoma

Adorni

Biolo

Zimetti

et al. 2022

IJMS

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Achilles tendon xanthoma (ATX) formation involves macrophage cholesterol accumulation within the tendon, similar to that occurring in atheroma. Macrophage cholesterol homeostasis depends on serum lipoprotein functions, namely the high-density lipoprotein (HDL) capacity to promote cell cholesterol efflux (cholesterol efflux capacity, CEC) and the serum cholesterol loading capacity (CLC). We explored the HDL-CEC and serum CLC, comparing 16 FH patients with ATX to 29 FH patients without ATX. HDL-CEC through the main efflux mechanisms mediated by the transporters ATP binding cassette G1 (ABCG1) and A1 (ABCA1) and the aqueous diffusion (AD) process was determined by a cell-based radioisotopic technique and serum CLC fluorimetrically. Between the two groups, no significant differences were found in terms of plasma lipid profile. A trend toward reduction of cholesterol efflux via AD and a significant increase in ABCA1-mediated HDL-CEC (+18.6%) was observed in ATX compared to no ATX patients. In ATX-presenting patients, ABCG1-mediated HDL-CEC was lower (−11%) and serum CLC was higher (+14%) compared to patients without ATX. Considering all the patients together, ABCG1 HDL-CEC and serum CLC correlated with ATX thickness inversely (p = 0.013) and directly (p < 0.0001), respectively. In conclusion, lipoprotein dysfunctions seem to be involved in ATX physiopathology and progression in FH patients.

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“…In terms of specific diseases, the HDL efflux 5):484-525, with permission from Elsevier) [47] capacity is negatively correlated with type 2 diabetes mellitus and to the incidence of CAD events, independent of other risk factors [65], although evidence of no association was reported in the CODAM Study in subjects with either elevated CVD risk or type 2 diabetes mellitus [66]. Conversely, CEC is impaired in individuals with familial hypercholesterolemia [67], systemic lupus erythematosus [68], nonalcoholic fatty liver disease [69], in women with polycystic ovary syndrome [70], or in individuals with hypogonadism or undergoing hormone affirming therapy [71][72][73]. In the context of CVD, the evaluation of HDL anti-inflammatory capacity is a functional metric, prospectively providing independent clinical information for the assessment of CVD, as in the case of Framingham Risk Score [74•].…”

Section: Hdl-the Functional Capacitymentioning

confidence: 99%

The Role of High-Density Lipoprotein Cholesterol in 2022

Sirtori

Corsini

Ruscica

2022

Curr Atheroscler Rep

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Purpose of the Review High-density lipoproteins (HDL) are responsible for the transport in plasma of a large fraction of circulating lipids, in part from tissue mobilization. The evaluation of HDL-associated cholesterol (HDL-C) has provided a standard method for assessing cardiovascular (CV) risk, as supported by many contributions on the mechanism of this arterial benefit. The present review article will attempt to investigate novel findings on the role and mechanism of HDL in CV risk determination. Recent Findings The most recent research has been aimed to the understanding of how a raised functional capacity of HDL, rather than elevated levels per se, may be responsible for the postulated CV protection. Markedly elevated HDL-C levels appear instead to be associated to a raised coronary risk, indicative of a U-shaped relationship. Summary While HDL-C reduction is definitely related to a raised CV risk, HDL-C elevations may be linked to non-vascular diseases, such as age-related macular disease. The description of anti-inflammatory, anti-oxidative and anti-infectious properties has indicated potential newer areas for diagnostic and therapeutic approaches. In the last two decades inconclusive data have arisen from clinical trials attempting to increase HDL-C pharmacologically or by way of recombinant protein infusions (most frequently with the mutant A-I Milano); prevention of stent occlusion or heart failure treatment have shown instead significant promise. Targeted clinical studies are still ongoing.

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The effect of transgender hormonal treatment on high density lipoprotein cholesterol efflux capacity

Cited by 20 publications

References 54 publications

Sex hormones drive changes in lipoprotein metabolism

Sex hormones drive changes in lipoprotein metabolism

HDL Cholesterol Efflux and Serum Cholesterol Loading Capacity Alterations Associate to Macrophage Cholesterol Accumulation in FH Patients with Achilles Tendon Xanthoma

The Role of High-Density Lipoprotein Cholesterol in 2022

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