HDL-C, ABCA1-mediated cholesterol efflux, and lipoprotein(a): insights into a potential novel physiologic role of lipoprotein(a)

Yeang, Calvin; Tsimikas, Sotirios

doi:10.1194/jlr.e060947

Cited by 3 publications

(4 citation statements)

References 47 publications

(25 reference statements)

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“…Like LDL particles, Lp(a) may act a role as an acceptor of cholesteryl esters from HDL particles 10 . Experimental data also suggest that Lp(a) can directly promote cholesterol efflux from HepG2 cells to HDL through upregulation of ABCA1 38,39 . Consistent with it, we found that the reduction in whole plasma CEC with evolocumab monotherapy was significantly associated with the corresponding reduction in plasma Lp(a) concentration (Figure 3), independent of LDL‐cholesterol, LDL‐apoB or apoB concentrations.…”

Section: Discussionsupporting

confidence: 74%

“…10 Experimental data also suggest that Lp(a) can directly promote cholesterol efflux from HepG2 cells to HDL through upregulation of ABCA1. 38,39 Consistent with it, we found that the reduction in whole plasma CEC with evolocumab monotherapy was significantly associated with the corresponding reduction in plasma Lp(a) concentration (Figure 3), independent of LDL-cholesterol, LDL-apoB or apoB concentrations. However, the lack of a significant association between the changes in whole plasma CEC and plasma Lp(a) concentration in patients with the combined treatment (i.e.…”

Section: Effect Of Evolocumab On Cholesterol Efflux Capacitysupporting

confidence: 77%

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Effect of a PCSK9 inhibitor and a statin on cholesterol efflux capacity: A limitation of current cholesterol‐lowering treatments?

Ying

Ronca

Chan

et al. 2022

Eur J Clin Investigation

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Background Cellular cholesterol efflux is a key step in reverse cholesterol transport that may impact on atherosclerotic cardiovascular risk. The process may be reliant on the availability of apolipoprotein (apo) B‐100‐containing lipoproteins to accept cholesterol from high‐density lipoprotein. Evolocumab and atorvastatin are known to lower plasma apoB‐100‐containing lipoproteins that could impact on cholesterol efflux capacity (CEC). Methods We conducted a 2‐by‐2 factorial trial of the effects of subcutaneous evolocumab (420 mg every 2 weeks) and atorvastatin (80 mg daily) for 8 weeks on CEC in 81 healthy, normolipidaemic men. The capacity of whole plasma and apoB‐depleted plasma, including ATP‐binding cassette transporter A1 (ABCA1)‐mediated and passive diffusion, to efflux cholesterol, was measured. Results Evolocumab and atorvastatin independently decreased whole plasma CEC (main effect p < .01 for both). However, there were no significant effects of evolocumab and atorvastatin on apoB‐depleted plasma, ABCA1‐mediated and passive diffusion‐mediated CEC (p > .05 in all). In the three intervention groups combined, the reduction in whole plasma CEC was significantly correlated with the corresponding reduction in plasma apoB‐100 concentration (r = .339, p < .01). In the evolocumab monotherapy group, the reduction in whole plasma CEC was also significantly correlated with the corresponding reduction in plasma lipoprotein(a) concentration (r = .487, p < .05). Conclusions In normolipidaemic men, evolocumab and atorvastatin decrease the capacity of whole plasma to efflux cellular cholesterol. These effects may be chiefly owing to a fall in the availability of apoB‐100‐containing lipoproteins. Reduction in circulating lipoprotein(a) may also contribute to the decrease in whole plasma cholesterol efflux with evolocumab monotherapy.

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Section: Discussionsupporting

confidence: 74%

Section: Effect Of Evolocumab On Cholesterol Efflux Capacitysupporting

confidence: 77%

Effect of a PCSK9 inhibitor and a statin on cholesterol efflux capacity: A limitation of current cholesterol‐lowering treatments?

Ying

Ronca

Chan

et al. 2022

Eur J Clin Investigation

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“…По нашим данным, у больных СГХС среди традиционных ФР основными, влияющими на риск развития ИБС, были курение, ожирение и уровень ЛПНП, который среди других показателей липидного спектра был определяющим (p=0,012). Изучение физио-логической роли ЛП (а), его влияния на риск развития сердечно-сосудистых заболеваний на сегодняшний день продолжается очень активно [1,13]. По нашим данным, уровень Лп(а) повышен у 41,9% больных СГХС.…”

Section: Discussionunclassified

Lipoprotein(a) Meaning as an Additional Marker of Cardiovascular Risk in Patients With Familial Hypercholesterolemia

Корнева¹,

Кузнецова²,

Tikhova³

2016

Russ J Cardiol

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Цель. Проанализировать взаимосвязь уровня Лп(а) и развития атеросклероза при семейной гиперхолестеринемии (СГХС). Материал и методы. Обследован 81 пациент с определенной СГХС, средний возраст -39,1±0,4 лет. Обследуемые были подразделены на 2 подгруппы: первая -с повышенным уровнем Лп(а) >0,3 г/л (34 человека); средний воз-раст -44,5±0,3; вторая -с нормальным уровнем Лп(а) <0,3 г/л (47 человек, 58,1%); средний возраст -37,5±0,3 лет. Результаты. Средний уровень Лп(а) у лиц разного возраста достоверно не различался. В обеих подгруппах практически у половины обследуемых выявлена артериальная гипертензия (АГ) (50,8% и 42,6%, соответственно), ожирение диагностировано у трети в обеих группах, количество курящих выше среди лиц с повышенным уровнем Лп(а) (11,8% и 8,5%). иБС диагностирована у 25,9% обследуемых. Частота иБС в подгруппе курения составила 44, 4%, в группе некурящих -25,8% (rr 1,72 (0,75; 3,99)), частота острого инфаркта миокарда (ОиМ) в подгруппе курения -44,6% против 13,5% (rr 3,26 (1,26; 8,43)). Среди показателей липидного спектра уровень ЛПНП был определяю-щим в развитии иБС (p=0,012). Наличие ожирения повышало риск иМ в 2,54 раза при СГХС (Ор 2,4 (1,05; 5,63)). При повышении уровня Лп(а) иБС диагно-стировалась чаще: 32,4% против 19%, но различия недостоверны (p=0,47). Частота ОиМ в первой группе была выше, чем во второй: 8 (23,5%) и 4 (8,5%), соответственно, (Ор 3,3 (1,1; 9,8), р=0,03). заключение. При СГХС на риск иБС влияли традиционные фр (курение, ожи-рение, и уровень ЛПНП). Aim. To analyze the relation of Lp(a) and atherosclerosis development in familial hypercholesterolemia (fHCe). Material and methods. Totally, 81 patient with definite fHCe studied, mean age 39,1±0,4 y. o. The participants were selected to two groups: first -with increased level of Lp(a) >0,3 g/L (n=34); mean age -44,5±0,3; second -with normal Lp(a) <0,3 g/L (n=47, 58,1%); mean age -37,5±0,3 y. o. Results. Mean level of Lp(a) in various age persons did not differ significantly. in both subgroups in about a half of all participants there was arterial hypertension (AH) revealed (50,8% and 42,6%, respectively), obesity was diagnosed in one third of both groups, number of smokers was higher in higher Lp(а) group (11,8% and 8,5%). iHd had 25,9% of participants. revalence of iHd in iHd group was 44, 4%, in non-smoker group -25,8% (rr 1,72 (0,75; 3,99)), acute myocardial infarction prevalence (Mi) in smoking subgroup was -44,6% versus 13,5% (rr 3,26 (1,26; 8,43)). Among lipid profile parameters LdL level was definitive for iHd development (p=0,012). Presence of obesity increased Mi risk 2,54 times in fHCe (Or 2,4 (1,05; 5,63)). With increase of Lp(a) iHd was diagnosed more commonly: 32, 4% versus 19%, non-significant (p=0,47). Prevalence of Mi in the first group was higher than in the second: 8 (23,5%) and 4 (8,5%), respectively, (Or 3,3 (1,1; 9,8), р=0,03). Conclusion. in fHCe, the risk of iHd was influenced by traditional rf (smoking, obesity, LdL level). Russ

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“…Lp(a) and oxPL are found in human atheromas, but more importantly, they are enriched in more advanced plaques compared with early lesions. MCP-1, an important chemokine implicated in the development of atherosclerosis, binds to oxidized LDL in an oxPL dependent manner, and is found on human Lp(a) as well [20, 22]. As a clinical correlate to these basic investigations, oxPLs measured on apo B‑100, which primarily reflect the content of oxPLs on Lp(a), strongly predicts anatomical disease in a variety of vascular beds as well as cardiovascular events such as cardiac death, MI, stroke, and peripheral arterial disease [22].…”

Section: Preventive Effects Of Lamentioning

confidence: 99%

Prevention of cardiovascular complications in patients with Lp(a)-hyperlipoproteinemia and progressive cardiovascular disease by long-term lipoprotein apheresis according to German national guidelines

Klingel

Heibges

Fassbender

2017

Clin Res Cardiol Suppl

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Lipoprotein(a) (Lp(a)) is an independent cardiovascular risk factor playing a causal role for atherosclerotic cardiovascular disease (CVD). Lipoprotein apheresis (LA) is a safe well-tolerated outpatient treatment to lower LDL-C and Lp(a) by 60–70%, and is the ultimate escalating therapeutic option in patients with hyperlipoproteinemias (HLP) involving LDL particles. Major therapeutic effect of LA is preventing cardiovascular events. Lp(a)-HLP associated with progressive CVD has been approved as indication for regular LA in Germany since 2008. The Pro(a)LiFe-study investigated with a prospective multicenter design the long-term preventive effect of LA on incidence rates of cardiovascular events prospectively over a period of 5 years in 170 consecutive patients who commenced regular LA. During a median period of 4.7 years of the pre-LA period, Lp(a) associated progressive CVD became apparent. Apolipoprotein(a) (apo(a)) isoforms and polymorphisms at the apo(a) gene (LPA) were analyzed to assess hypothetical clinical correlations. 154 patients (90.6%) completed 5‑years follow-up. Significant decline of the mean annual major adverse cardiac event (MACE) rate was observed from 0.41 ± 0.45 two years prior to regular LA to 0.06 ± 0.11 during 5 years with regular LA (p < 0.0001). 95.3% of patients expressed at least one small apo(a) isoform. Calculation of isoform specific concentrations allowed to confirm the equivalence of 60 mg/dl or 120 nmol/l as Lp(a) thresholds of the German LA guideline. Results of 5 years prospective follow-up confirmed that LA has a lasting effect on prevention of cardiovascular events in patients with Lp(a)-HLP and afore progressive CVD.

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HDL-C, ABCA1-mediated cholesterol efflux, and lipoprotein(a): insights into a potential novel physiologic role of lipoprotein(a)

Cited by 3 publications

References 47 publications

Effect of a PCSK9 inhibitor and a statin on cholesterol efflux capacity: A limitation of current cholesterol‐lowering treatments?

Effect of a PCSK9 inhibitor and a statin on cholesterol efflux capacity: A limitation of current cholesterol‐lowering treatments?

Lipoprotein(a) Meaning as an Additional Marker of Cardiovascular Risk in Patients With Familial Hypercholesterolemia

Prevention of cardiovascular complications in patients with Lp(a)-hyperlipoproteinemia and progressive cardiovascular disease by long-term lipoprotein apheresis according to German national guidelines

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