Prognostic Usefulness of Serum Cholesterol Efflux Capacity in Patients With Coronary Artery Disease

Zhang, Jianhua; Xu, Jianrong; Wang, Jingfeng; Wu, Changhao; Yan, Xu; Wang, Yueguo; Deng, Fengfeng; Wang, Zhe; Chen, Xuhua; Wu, Mengzuo; Chen, Yangxin

doi:10.1016/j.amjcard.2015.11.033

Cited by 26 publications

(39 citation statements)

References 24 publications

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“…Обратная связь ХС-акцепторной способности плазмы с выраженностью ИБС показана в 2015-2016 гг. в более 10 клинических исследованиях -как у пациентов, проходивших амбулаторное лечение или обследование, так и в условиях госпитализации [7,8,[11][12][13][14][15][16][17]. В отношении связи этого показателя c уровнем ХС ЛВП результаты противоречивы.…”

Section: активность выведения клеточного хс у больных коронарным атерunclassified

“…Это указывает как на роль уровня ХС ЛВП КЛИНИЧЕСКИЕ СЕМИНАРЫ § в сыворотке крови, так и на его недостаточность и наличие других влияющих факторов. В целом способность ЛВП плазмы крови акцептировать ХС из клеток оказывается ценным диагностическим критерием оценки риска развития ИБС и может служить, по мнению многих авторов, новым информативным биомаркером [11][12][13][14][15][16][17].…”

Section: активность выведения клеточного хс у больных коронарным атерunclassified

“…Предполагают возможное действие ряда факторов, содержащихся в плазме помимо ЛВП и косвенно коррелирующих с активностью выведения ХС, например, влияние альбумина [19] или сывороточного амилоида SAA [20]. Кроме того, в данном исследовании не оценивали общего выхода ХС (помимо опосредованного АВСА1) [10], и число больных (n=113) считают относительно небольшим по сравнению с таковым в других работах [11][12][13][14][15][16][17]. Отмечают важность дальнейших исследований в этой области -для выяснения еще не полностью изученных процессов и взаимодействий [10].…”

Section: активность выведения клеточного хс у больных коронарным атерunclassified

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Dysfunctional High-Density Lipoproteins: Role in Atherogenesis and Potential Targets for Phospholipid Therapy

Torchovskaya

Kudinov

Zakharova

et al. 2018

CARDIO

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Резюме В последние годы резко увеличилось число публикаций, посвященных нарушениям у больных атеросклерозом свойств липопротеинов высокой плотности (ЛВП)-в первую очередь способности акцептировать холестерин (ХС) из макрофагов, лежащей в основе их антиатерогенного действия. Это свойство оценивали ex vivo-по активности выхода ХС из клеток к ЛВП или в сыворотку обследуемых больных. Показана обратная связь ХС-акцепторной активности ЛВП с тяжестью атеросклеротического заболевания или частотой его обострения в течение длительных периодов наблюдения, независимо от концентрации ХС ЛВП. Результаты этих исследований привели к появлению концепции о важности «не только количества, но и качества ЛВП», т. е. их функциональности. В настоящем обзоре рассмотрены пути выведения ХС из клеток (с участием клеточных белков), методические подходы, используемые для выявления дисфункциональных ЛВП, результаты исследований у различных категорий больных. Приведены данные разных авторов по выявлению механизмов нарушений свойств ЛВП путем изучения их состава, включая протеомные и липидомные подходы. Определенных доказанных мишеней для коррекции дисфункциональности ЛВП в настоящее время нет. Единственный фактор, отмечаемый многими авторами, это существенная роль фосфолипидов (ФЛ) ЛВП, уровень которых коррелирует с активностью выведения клеточного ХС. Это позволяет по-новому взглянуть на применявшуюся ранее фосфолипидную терапию атеросклероза. Механизм ее заключается, по-видимому, не в снижении уровня ХС в плазме крови, как ожидалось, а в улучшении антиатерогенных свойств ЛВП. Для практического ее применения необходима разработка принципиально новых композиций с высокой биодоступностью ФЛ, обогащающих ЛВП, нормализуя их способность к выведению ХС из тканей.

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Section: активность выведения клеточного хс у больных коронарным атерunclassified

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Dysfunctional High-Density Lipoproteins: Role in Atherogenesis and Potential Targets for Phospholipid Therapy

Torchovskaya

Kudinov

Zakharova

et al. 2018

CARDIO

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“…CEC has been shown to be associated with reduced intima-media thickness indicating that it promotes the removal of cholesterol from arterial wall macrophages . Prospective studies have shown that CEC is a predictor for CVD, independent of HDL-C [Rohatgi et al 2014, Saleheen et al 2015, Zhang et al 2016. There is, however, a study showing that CEC was inversely associated with prevalent CVD, but positively associated with incident CVD (in contrast to the other studies) [Li et al 2013].…”

Section: Cholesterol Efflux Capacity Assaymentioning

confidence: 61%

“…The cells are plated and cultured in wells before being loaded with labeled cholesterol. The labeling is commonly accomplished using radiolabeled 3 H or 14 Ccholesterol , Zhang et al 2016] but a method using fluorescence-labeled cholesterol has been described [Rohatgi et al 2014]. ApoB-depleted plasma is added to the cells and incubated to allow uptake of cholesterol to HDL/apoA-I in the media.…”

Section: Cholesterol Efflux Capacity Assaymentioning

confidence: 99%

Lipoproteomics Environmental and Genetic Factors Affecting High-Density Lipoprotein (HDL)

Ljunggren¹

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Lipoprotein particles act as lipid transporters in the blood stream, and measuring cholesterol content in specific subclasses of lipoprotein particles has long been, and still is, a frequently used tool to estimate the risk of cardiovascular disease (CVD). High-density lipoprotein (HDL) is a subclass of lipoproteins often regarded as providing protection against CVD via several functions including reverse cholesterol transport and antiinflammatory capacities. However, the precise relationship between HDL cholesterol levels and health outcome is still unclear. Lately, new approaches to study HDL composition and function have therefore become more important.HDL function is to a large extent dependent on its proteome, containing more than 100 proteins. Investigating the proteome in individuals with altered gene expression for HDLassociated proteins or with known exposure to environmental contaminants may reveal new insights into how HDL metabolism is affected by various factors. This is of interest in order to better understand the role of HDL in CVD.Papers I and II focus on two different mutations in a structural HDL protein, apolipoprotein A-I (L202P and K131del), and one mutation in the scavenger receptor class B-1 (P297S), which is involved in selective lipid uptake of cholesterol mainly into hepatocytes and adrenal cells. The HDL proteome was analyzed using two-dimensional gel electrophoresis and mass spectrometry. The L202P mutation was identified in HDL of the heterozygote carriers together with a significant decrease of apolipoprotein E and increased zinc-alpha-2-glycoprotein. By contrast, the second apolipoprotein A-I mutation (K131del) was associated with significantly elevated alpha-1-antitrypsin and transthyretin levels. Protein analyses of the scavenger receptor class B1 P297S heterozygotes showed a significant increase in HDL apoL-1 along with increased free apoE. The carriers showed no difference in anti-oxidative capability but a significant increase in apoA-I methionine oxidation.Papers III and IV focus on persistent organic pollutants that may influence HDL composition and function. These compounds accumulate in humans, and exposure has been linked to an increased risk of CVD. To provide a better understanding of the HDL system in relation to pollutants, a population living in a contaminated area was studied. Persistent organic pollutants in isolated HDL were quantified using high-resolution gas chromatography mass spectrometry and significantly increased levels were found in individuals with CVD as compared to healthy controls. Furthermore, there was a significant negative association between the pollutants and paraoxonase-1 anti-oxidant activity. Studying the proteome with nano-liquid chromatography tandem mass ii spectrometry led to the identification of 118 proteins in HDL, of which ten were significantly associated with the persistent organic pollutants. In summary, the present studies demonstrate protein pattern alterations in HDL associated with inherited genetic variants or polluta...

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Moderate Renal Impairment Does Not Impact the Ability of CSL112 (Apolipoprotein A‐I [Human]) to Enhance Cholesterol Efflux Capacity

Gille¹,

Duffy

Tortorici

et al. 2018

The Journal of Clinical Pharma

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CSL112 (apolipoprotein A‐I [human]) is a novel intravenous formulation of plasma‐derived apolipoprotein A‐I (apoA‐I) that enhances cholesterol efflux capacity. Renal impairment is a common comorbidity in acute myocardial infarction patients and is associated with impaired lipid metabolism. The aim of this phase 1 study was to assess the impact of moderate renal impairment on the pharmacokinetic and pharmacodynamic profile of CSL112. Sixteen subjects with moderate renal impairment and 16 age‐, sex‐, and weight‐matched subjects with normal renal function participated in the study. Within each renal function cohort, subjects were randomized 3:1 to receive a single intravenous infusion of CSL112 2 g (n = 6) or placebo (n = 2) or CSL112 6 g (n = 6) or placebo (n = 2). At baseline, subjects with moderate renal impairment versus normal renal function had higher total cholesterol efflux, ABCA1‐dependent cholesterol efflux capacity, and pre‐β1‐high‐density lipoprotein (HDL) levels. Infusing CSL112 resulted in similar, immediate, robust, dose‐dependent elevations in apoA‐I and cholesterol efflux capacity in both renal function cohorts and significantly greater elevations in pre‐β1‐HDL ( P < .05) in moderate renal impairment. Lecithin‐cholesterol acyltransferase activity, demonstrated by a time‐dependent change in the ratio of unesterified to esterified cholesterol, did not differ by renal function. No meaningful changes in proatherogenic lipid levels were observed. Moderate renal impairment did not impact the ability of CSL112 to enhance cholesterol efflux capacity. CSL112 may represent a novel therapy to reduce the risk of early recurrent cardiovascular events following acute myocardial infarction in patients with or without moderate renal impairment.

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Prognostic Usefulness of Serum Cholesterol Efflux Capacity in Patients With Coronary Artery Disease

Cited by 26 publications

References 24 publications

Dysfunctional High-Density Lipoproteins: Role in Atherogenesis and Potential Targets for Phospholipid Therapy

Dysfunctional High-Density Lipoproteins: Role in Atherogenesis and Potential Targets for Phospholipid Therapy

Lipoproteomics Environmental and Genetic Factors Affecting High-Density Lipoprotein (HDL)

Moderate Renal Impairment Does Not Impact the Ability of CSL112 (Apolipoprotein A‐I [Human]) to Enhance Cholesterol Efflux Capacity

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