ABCA1-dependent serum cholesterol efflux capacity inversely correlates with pulse wave velocity in healthy subjects

Favari, Elda; Ronda, Nicoletta; Adorni, Maria Pia; Zimetti, Francesca; Salvi, Paolo; Manfredini, Matteo; Borghi, Claudio; Cicero, Arrigo F G

doi:10.1194/jlr.p030452

Cited by 35 publications

(22 citation statements)

References 49 publications

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“…We did not perform a structural characterization of HDL subpopulations in this present work, but based on Berrougui's findings, we may hypothesize that the HDL 2 contribution to cholesterol efflux may compensate for the HDL 3 impairment, possibly justifying the improved CEC observed in our subjects. In addition, in Berrougui's work the isolation of HDL was performed with ultracentrifuge that caused the elimination of nascent pre-beta HDL particles, as the authors themselves state, that are well known efficient acceptors of cholesterol released through ABCA1 and ABCG1 (44,45), both expressed in the cellular model that we have adopted (18). Conversely, in our samples it is conceivable that prebeta HDL significantly contribute to increased CEC by these mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…We finally compared serum CEC values of elderly subjects with those obtained from a cohort of sex-matched, free of cardiovascular events, middle-aged individuals (n = 140) that we analyzed in a previous study (18), whose demographic and clinical characteristics are reported in Table 2.…”

Section: Resultsmentioning

confidence: 99%

“…A growing number of evidence indicates an inverse relationship between HDL CEC and both the prevalence and the incidence of CVD (17)(18)(19). Interestingly, this association has been found to persist even after adjustment for traditional risk factors including HDL-C plasma levels, suggesting that HDL function may represent a predictor of CVD transcending the risk estimation based solely on the amount of particles present in the bloodstream.…”

Section: Introductionmentioning

confidence: 99%

“…Serum CEC results relative to middle-aged subjects included in the present work belong to a previous published study (18) and were selected among a database of the Brisighella Heart Study (25), for which the approval by the Ethical Committee of the University of Bologna was obtained. All protocols were in accordance with the ethical standards of the Helsinki Declaration, with all participants having signed informed consent before enrollment.…”

Section: Subjectsmentioning

confidence: 99%

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Cholesterol efflux capacity does not associate with coronary calcium, plaque vulnerability, and telomere length in healthy octogenarians

Zimetti

Freitas

Campos

et al. 2018

Journal of Lipid Research

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RUNNING TITLECholesterol efflux capacity and atherosclerosis in elderly. ABBREVIATIONSANCOVA, analysis of covariance; CAC, coronary artery calcium; CEC, cholesterol efflux capacity; CRP, Creactive protein; HDL-C, HDL cholesterol; FMD, flow mediated dilation; IMT, intima-media thickness; LDL-C, LDL cholesterol; TC, total cholesterol; TL, telomere length; WHO, world health organization. AbstractSeveral studies revealed that traditional risk factors are less effective in predicting CVD risk in the elderly, suggesting the need to identify new biomarkers. Here we evaluated the association between serum cholesterol efflux capacity (CEC), an atheroprotective property of HDL recently identified as a novel marker of CVD risk, and atherosclerotic burden in a cohort of very old, healthy individuals. Serum CEC values were not significantly correlated neither with calcium score nor with markers of vulnerable plaque, such as positive remodeling, hypodensity, spotty calcification or napking-ring sign. In addition, no association was detected between CEC and telomere length, a marker of biological aging that has been linked to atherosclerosis extent. Interestingly, elderly subjects presented a remarkably higher CEC (+30.2%; p<0.0001) compared to values obtained from a cohort of sex-matched, free of cardiovascular events, middle-aged individuals. In conclusion, serum CEC is not related to traditional risk factors in very old, free of cardiovascular events subjects, but has significantly higher values compared to a healthy, younger population. Whether this improved HDL functionality may represent a protective factor in CVD onset has to be established in future studies.

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Section: Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Subjectsmentioning

confidence: 99%

See 2 more Smart Citations

Cholesterol efflux capacity does not associate with coronary calcium, plaque vulnerability, and telomere length in healthy octogenarians

Zimetti

Freitas

Campos

et al. 2018

Journal of Lipid Research

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“…HDL cholesterol efflux capacity was quantified using a validated ex vivo assay that measures the ability of apolipoprotein-B depleted serum to mobilize cholesterol from cholesterol-laden macrophages [23,[28][29][30][31]. J774 cells, a mouse macrophage cell line [32], were plated and labeled for 24 hours with 1 μCi/mL Hcholesterol efflux was determined by incubating cells with 2.8% apoB-depleted serum for 4 hours as described [28].…”

Section: Measurements Of Hdl Cholesterol Efflux Capacitymentioning

confidence: 99%

Metrics of high-density lipoprotein function and hospital mortality in acute heart failure patients

et al. 2016

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ObjectiveThe functionality of high-density lipoprotein (HDL) is impaired in chronic ischaemic heart failure (HF). However, the relationship between HDL functionality and outcomes in acute HF (AHF) has not been studied. The present study investigates whether the metrics of HDL functionality, including HDL cholesterol efflux capacity and HDL-associated paraoxonase (PON)-1 arylesterase (AE) activity are associated with hospital mortality in AHF patients. Methods and ResultsThe study was performed as a prospective, single-centre, observational research on 152 patients, defined and categorised according to the ESC and ACCF/AHA Guidelines for HF by time of onset, final clinical presentation and ejection fraction. The mean age of the included patients (52% female) was 75.2 years (SD 10.3) and hospital mortality was 14.5%. HDL cholesterol efflux capacity was examined by measuring the capacity of apoB depleted serum to remove tritium-labelled cholesterol from cultured macrophages. The AE activity of the HDL fraction was examined by a photometric assay. In a univariable regression analysis, low cholesterol efflux, but not AE activity, was significantly associated with hospital mortality [odds ratio (OR) 0.78, 95% confidence interval (CI) 0.64-0.96, p = 0.019]. In multivariable analysis progressively adjusting for important clinical and laboratory parameters the association obtained for cholesterol efflux capacity and hospital mortality by univariable analysis, despite a stable OR, did not stay significant (p = 0.179). ConclusionOur results suggest that HDL cholesterol efflux capacity (but not AE activity) contributes to, but is not an independent risk factor for, hospital mortality in AHF patients. Larger studies are needed to draw firm conclusions.

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Newly Identified Antiatherosclerotic Activity of Methotrexate and Adalimumab: Complementary Effects on Lipoprotein Function and Macrophage Cholesterol Metabolism

Ronda

Greco

Adorni

et al. 2015

Arthritis & Rheumatology

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Objective Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis. The reduction in cardiovascular risk that is induced by methotrexate (MTX) and anti–tumor necrosis factor α agents in RA is considered secondary to their anti‐inflammatory action, but their effects on serum lipoprotein function and foam cell formation are unknown. The reduced capacity of high‐density lipoprotein (HDL) to promote cell cholesterol efflux and the increased serum cell cholesterol‐loading capacity (CLC) demonstrated in RA may contribute to foam cell development. The aim of this study was to investigate the influence of MTX and adalimumab treatment on serum cholesterol efflux capacity (CEC) and CLC in RA patients and to study the in vitro effects of the two drugs on macrophage cholesterol handling. Methods Sera from RA patients treated with MTX (n = 34) or with adalimumab and MTX (n = 22) obtained before treatment, after 6 weeks of treatment, and after 6 months of treatment were analyzed for CEC and CLC by radioisotopic and fluorometric techniques, respectively. The influence of MTX and adalimumab on macrophage cholesterol efflux and uptake was evaluated in vitro using human THP‐1–derived macrophages. Results MTX treatment was associated with increases in serum HDL, low‐density lipoprotein, and total cholesterol levels and with ATP‐binding cassette G1–mediated and scavenger receptor class B type I (SR‐BI)–mediated increases in CEC; MTX treatment was not associated with modifications in CLC. Adalimumab treatment was associated with increases in serum HDL levels, a transient increase in SR‐BI–mediated CEC, a transient decrease in ATP‐binding cassette A1–mediated CEC, and a significant reduction in CLC; in addition, adalimumab reduced macrophage cholesterol uptake in vitro. Conclusion Antiatherosclerotic activity asso‐ciated with MTX and adalimumab may be mediated by beneficial and complementary effects on lipoprotein functions and on macrophage cholesterol handling. As a whole, these mechanisms may oppose foam cell formation.

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ABCA1-dependent serum cholesterol efflux capacity inversely correlates with pulse wave velocity in healthy subjects

Cited by 35 publications

References 49 publications

Cholesterol efflux capacity does not associate with coronary calcium, plaque vulnerability, and telomere length in healthy octogenarians

Cholesterol efflux capacity does not associate with coronary calcium, plaque vulnerability, and telomere length in healthy octogenarians

Metrics of high-density lipoprotein function and hospital mortality in acute heart failure patients

Newly Identified Antiatherosclerotic Activity of Methotrexate and Adalimumab: Complementary Effects on Lipoprotein Function and Macrophage Cholesterol Metabolism

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