Role of apolipoproteins A-I, A-II and C-I in cholesterol efflux from endothelial and smooth muscle cells

The role of purified apolipoproteins A-I, A-II and C-fin theprocess of cholesterol efflux from cultured vascular endothelialand smooth muscle cells was studied [³H] Cholesterol pre-labelledcultures were exposed to serum-free medium supplemented withfree apolipoproteins or with apolipoproteins and phosphatidylcholineliposomes and the cholesterol efflux from the cells was determined.Free apolipoproteins A-I and A-II supported cholesterol effluxfrom vascular endothelial and smooth muscle cells to a higherextent than apolipoprotein C-I. The ability of free apolipoproteinsA-I and A-II to support cholesterol efflux was in correlationwith their specific binding to the cultures, while no specficbinding of apolipoprotein C-I was detected. The associationof apolipoprotein A-I with phosphatidylcholine liposomes resultedin a more than two-fold increase in cholesterol efflux comparedto free apolipoprotein A-I, while association of apolipoproteinsA-Il and C-I with phosphatidylcholine liposomes resulted ina very limited increase in cholesterol efflux above that achievedby the free apolipoproteins. These results suggest that apolipoprotein A-I is involved incholesterol efflux performed by high density lipoprotein. Furthermore,free apolipoproteins A-I and A-II, but not apolipoprotein C-Imay take an active part in cholesterol efflux from endothelialand smooth muscle cells.     

Evidence for a lipoprotein carrier in human plasma catalyzing sterol efflux from cultured fibroblasts and its relationship to lecithin:cholesterol acyltransferase

Immunoaffinity chromatography has been used to study the determinants of sterol efflux and net transport from cultured fibroblasts to human plasma medium. Sterol efflux was highly (approximately 80%) dependent upon a minor lipoprotein fraction containing apolipoprotein A-I unassociated with other apolipoproteins. The remaining activity was associated with the lipoprotein-free fraction of plasma and could be replaced by apoprotein-free albumin. Efflux was independent of lecithin:cholesterol acyltransferase (EC 2.3.1.43) activity. Net transport (i.e., the excess of efflux over influx) was completely inhibited by inhibition of lecithin:cholesterol acyltransferase or its removal by affinity chromatography on immobilized antibodies to apolipoprotein A-I or D (components of the transfer complex in human plasma). In uninhibited plasma, efflux and net transport rates had similar kinetics, suggesting that these were linked functions and that net transport was initiated by a carrier-dependent efflux step that, in the absence of lecithin:cholesterol acyltransferase activity, was associated with an equivalent influx of free sterol to the cells and that, in the presence of lecithin:cholesterol acyltransferase, was associated with esterification and transfer protein activity. The cholesterol carrier lipoprotein function (approximately 5% of plasma apolipoprotein A-I) appears to be the first step of lecithin:cholesterol acyltransferase-linked sterol transport from cells.     

Tissue-specific PKA inhibition using a chemical genetic approach and its application to studies on sperm capacitation

Studies on cAMP signaling and protein kinase A (PKA) function in vivo are limited by the lack of highly specific inhibitors that can be used in primary cell culture and whole animals. Previously we reported that a mutation in the ATP binding pocket of a catalytic subunit (Cα) of PKA confers sensitivity to the pyrazolo[3,4-d]pyrimidine inhibitor, 1NM-PP1. We have now engineered the mouse Pkraca gene such that after Cre-mediated recombination in vivo, the CαM120A mutant protein is expressed and the wild-type Cα is turned off. We demonstrate the utility of this approach by examining the requirement for PKA activity during capacitation of sperm from mice that express CαM120A mutant protein. For CαM120A sperm, 10 μM of 1NM-PP1 prevented PKA-dependent phosphorylation and the activation of motility that are both rapidly (<90 s) evoked by the HCO₃⁻ anion. A continuous (90 min) inhibition with 10 μM of 1NM-PP1 prevented the protein tyrosine phosphorylation of late-stage capacitation. Delayed application of 1NM-PP1 demonstrated that PKA activity was required for at least the initial 30 min of capacitation to produce subsequent protein tyrosine phosphorylation. Acute application of 1NM-PP1 rapidly slowed the accelerated beat of activated motility but did not affect the established waveform asymmetry of hyperactivated sperm. Our results demonstrate that PKA in CαM120A mutant sperm is rapidly and reversibly inhibited by 1NM-PP1 and that this blockade has selective and time-dependent effects on multiple aspects of capacitation. The conditional CαM120A-expressing mouse lines will be valuable tools for studying PKA function in vivo.     

Timing of fertilization in mammals: sperm cholesterol/phospholipid ratio as a determinant of the capacitation interval.

A survey of species differences in the duration of capacitation, T, has revealed that they closely correlate with sperm cholesterol/phospholipid mole ratios, R : T = 8R - 1 (r2 = 0.97, in which r is Pearson's correlation coefficient). Because uterine cells displayed low relative cholesterol concentrations, spermatozoa evidently experience a negative external cholesterol gradient (positive phospholipid gradient) during capacitation. A decrease in sperm R-value is suggested, therefore, to accompany capacitation. The idea received strong support from a kinetic analysis of capacitation intervals, based on the rate of cholesterol efflux from sperm cells in utero. Lipid-binding serum proteins in uterine fluid are attributed with removing a sterol barrier to the Ca2+-facilitated membrane fusion that initiates the acrosome reaction. Tight cell junctions prevent permeation of the male generative tract by these proteins (capacitation factors). Furthermore, seminal plasma contains a decapacitation factor, identified as a membrane vesicle (cholesterol donor) component of this fluid, that reverses capacitation. Initiation of the sperm acrosome reaction among mammals could be the first fusion process found to be physiologically modulated through the membrane bilayer cholesterol level.     

Sperm capacitation is regulated by the crosstalk between protein kinase A and C

The binding of capacitated sperm to the egg's zona pellucida stimulates it to undergo the acrosome reaction, a process which enables the sperm to penetrate the egg. Mammalian sperm capacitation and the acrosome reaction require remodeling of actin filaments. An increase in phospholipase D (PLD)-dependent actin polymerization occurs during capacitation whereas the increase in sperm intracellular calcium after its binding to the egg causes very fast actin depolymerization prior to the acrosome reaction. Protein kinase A (PKA) and C (PKC) can both activate sperm PLD and actin polymerization under in vitro incubation, however under physiological conditions, actin polymerization depends primarily on PKA activity. We suggest that PKA indirectly activates phosphatidylinositol 4-kinase to produce phosphatidylinositol 4,5-bisphosphate which is a cofactor for PLD activation. In addition, activation of PKA during capacitation inactivates phospholipase C resulting in preventing PKC activation. It appears that PKA activation promotes sperm capacitation whereas too early activation of PKC during capacitation would jeopardize this process. Thus, a refined balance between the two pathways is required for optimal and sustained activation during sperm capacitation.     

Altered lipid, apolipoprotein, and lipoprotein profiles in inflammatory bowel disease: consequences on the cholesterol efflux capacity of serum using Fu5AH cell system

Epidemiological data suggest a link between chronic inflammation condition and atherosclerosis. Infection and inflammation can also impair lipoprotein metabolism and produce a wide variety of changes in plasma concentrations of lipids and lipoproteins. Twenty-one patients with inflammatory bowel diseases (IBDs) and 28 healthy subjects were recruited. Serum concentrations of lipids, lipoproteins, apolipoproteins, leptin, ghrelin, and inflammation markers (C-reactive protein and serum amyloid A) were measured, and subjects' lipoproteins were characterized. The ability of patients with serum IBD to efflux free cell cholesterol was measured. Serum cholesterol, high-density lipoprotein cholesterol, apolipoprotein (apo) A-I, apoC-II, apoC-III bound to apoB, phospholipid, and phospholipids not bound to apoB levels were significantly lower, whereas serum triglyceride, serum amyloid A, and C-reactive protein levels were significantly higher in patients with active IBD. Apolipoprotein A-I immunoreactivity (pre-beta small particles and small alpha-high-density lipoprotein particles) is decreased in patients with IBD. In contrast, apoE immunoreactivity (slow/small apoE containing lipoprotein particles [LpE particle]) increased in these patients. The efflux capacity of serum from patients with IBD using [(3)H]-cholesterol-labeled Fu5AH cells was reduced (P < .005). Our results demonstrate that, in subjects with active IBD, inflammation leads to alterations in lipid, apolipoprotein, and lipoprotein profiles and reduced cholesterol efflux. These changes are similar to those proposed to promote atherogenesis and may contribute to the development of cardiovascular events.     

Specific mutations in ABCA1 have discrete effects on ABCA1 function and lipid phenotypes both in vivo and in vitro

Mutations in ATP-binding cassette transporter A1 (ABCA1) cause Tangier disease and familial hypoalphalipoproteinemia, resulting in low to absent plasma high-density lipoprotein cholesterol levels. However, wide variations in clinical lipid phenotypes are observed in patients with mutations in ABCA1. We hypothesized that the various lipid phenotypes would be the direct result of discrete and differing effects of the mutations on ABCA1 function. To determine whether there is a correlation between the mutations and the resulting phenotypes, we generated in vitro 15 missense mutations that have been described in patients with Tangier disease and familial hypoalphalipoproteinemia. Using localization of ABCA1, its ability to induce cell surface binding of apolipoprotein A-I, and its ability to elicit efflux of cholesterol and phospholipids to apolipoprotein A-I we determined that the phenotypes of patients correlate with the severity and nature of defects in ABCA1 function.     

Molecular regulation of macrophage reverse cholesterol transport

PURPOSE OF REVIEW: Macrophage reverse cholesterol transport is one of the key mechanisms mediating the protective effects of high-density lipoproteins on atherosclerosis. This review focuses on the recent developments in our understanding of molecular mechanisms of macrophage reverse transport and regulators that play important roles during this process. RECENT FINDINGS: Macrophage reverse cholesterol transport is promoted by apolipoprotein A-I overexpression and reduced in the setting of apolipoprotein A-I deficiency. A liver X receptor agonist markedly increases macrophage reverse cholesterol transport. ATP-binding cassette transporter A1 and ATP-binding cassette transporter G1 are liver X receptor-responsive macrophage genes that promote cholesterol efflux to lipid-free apolipoprotein A-I and mature high-density lipoprotein, respectively. The direct roles of ATP-binding cassette transporter A1 and ATP-binding cassette transporter G1 in macrophage reverse cholesterol transport in vivo remain unclear. Therapeutically promoting macrophage reverse cholesterol transport has been recognized as one of the promising means to prevent atherosclerosis. SUMMARY: Increasing evidence has suggested that ATP-binding cassette transporter A1 and ATP-binding cassette transporter G1 are involved in macrophage reverse cholesterol transport. In-depth understanding of the molecular mechanisms will enable us to develop new therapeutic means to protect against atherosclerosis.     

Leptin secretion by human ejaculated spermatozoa

INTRODUCTION: Leptin action is a dynamic area of investigation that continues to broaden beyond the basic lipostatic model originally envisaged. Here, we show that leptin is expressed in and secreted from human ejaculated spermatozoa. METHODS: By RT-PCR, Western blot, and immunofluorescence techniques, we have demonstrated that human sperm express leptin. RIA method evidenced leptin secretion. Phosphatidyl-inositol-kinase-3 (PI3K)/Akt pathway was examined by PI3K activity assay and Western blot. Leptin and insulin regulation of glycogen synthesis was evaluated by glycogen synthase activity (GSA). RESULTS: The large differences of leptin secretion between uncapacitated and capacitated sperm suggest a functional role for leptin in capacitation. Indeed, in uncapacitated sperm, leptin enhances both cholesterol efflux and protein tyrosine phosphorylation. In uncapacitated sperm, both insulin and leptin increased PI3K activity, Akt S473, and glycogen synthase kinase-3 S9 phosphorylation. Interestingly, during capacitation, concomitantly to the massive release of both hormones, we observed a strong reduction in the phosphorylation of glycogen synthase kinase-3 S9, kinase downstream of Akt that regulates the glycogen synthase. Our results from GSA showed that the enzymatic activity was significantly higher in uncapacitated than in capacitated sperm. Particularly, in uncapacitated sperm, GSA appeared to depend on the hormones concentration, because the enzymatic activity was stimulated at low doses, whereas it was inhibited at high doses. Moreover, both leptin and insulin regulate in autocrine fashion sperm glycogen synthesis. CONCLUSION: Leptin secretion by sperm suggests that the male gamete may be able to modulate its metabolism independently by systemic leptin. These data open new considerations about leptin significance in male fertility.     

The mitochondrial citrate carrier (CIC) is present and regulates insulin secretion by human male gamete

The mechanisms through which sperm manage their energy metabolism are poorly understood. The present study provides biochemical and morphological evidence that mitochondrial citrate carrier (CIC) is present in ejaculated human sperm and is restricted to the midpiece. The inhibition of CIC with the specific substrate analog 1,2,3-benzenetricarboxylate resulted in the reduction of cholesterol efflux, protein tyrosine phosphorylation, phospho-AKT, phospho-p60src, hyperactivated motility and acrosome reaction, suggesting a role for this mitochondrial carrier in sperm physiology. Furthermore, inhibition of CIC by 1,2,3-benzenetricarboxylate resulted in a reduction of glucose-stimulated insulin secretion and autocrine insulin secretion by sperm. Remarkably, blocking CIC also reduced glucose-6-phosphate dehydrogenase activity, probably in accordance with its regulation on insulin secretion. Capacitation and glucose metabolism were stimulated by glucose as well as citrate, the specific substrate of CIC, implying a similar action because glucose and citrate both induced insulin secretion by sperm. In the present finding, we discovered a new site of action for CIC in the regulation of metabolism, and it may be assumed that CIC works with other factors in the regulation of sperm energy metabolism to sustain capacitation process and acrosome reaction.     

High levels of human apolipoprotein A-I and high density lipoproteins in transgenic mice do not enhance efflux of cholesterol from a depot of injected lipoproteins. Relevance to regression of atherosclerosis?

The role of high density lipoprotein (HDL) and apolipoprotein A-I (apo A-I)in promoting cholesterol efflux from cultured cells and attenuation of development of atherosclerosis in transgenic (tg) animals has been well documented. The aim of the present study was to determine whether high levels of human (h) apo A-I will enhance cholesterol removal in vivo. h apo A-I in sera of tg mice was 429 +/- 18 and 308 +/- 10 mg/dl in male and female mice, the ratio of phospholipid (PL) to apo A-I was 0.94 in tg and 2.4 and 1.9 in male and female controls, taking mouse apo A-I as 100 mg/dl. The removal of lipoprotein cholesterol injected in the form of cationized low density lipoprotein (cat-LDL) into the rectus femoris muscle of h apo A-I tg is compared with control mice. After injection of cat-LDL labeled with [3H]cholesterol, the labeled cholesterol was cleared from the depot with a t 1/2 of about 4 days in both control and tg mice. The clearance of the exogenous cholesterol mass was initially much slower, it approached the t 1/2 of about 4 days between day 8 and 14 but there was no difference between tg and control mice. Cholesterol efflux from cultured macrophages exposed to media containing up to 10% serum was 56% higher with serum from tg mice than controls. In conclusion, the efflux of cholesterol from a localized depot of cat-LDL was not enhanced in h apo A-I tg mice. It appears, therefore, that while an increase above physiological levels of apo A-I or plasma HDL does play a pivotal role in the prevention of initiation and progression of early stages of atherosclerosis, the effectiveness of such an increase for the regression stage remains still to be demonstrated.     

Sequential estrogen-progestin replacement therapy in healthy postmenopausal women: effects on cholesterol efflux capacity and key proteins regulating high-density lipoprotein levels

Thirty healthy postmenopausal women were randomized into 2 groups that received a sequential combined hormone-replacement therapy (HRT) (n = 18; conjugated equine estrogen 0.625 mg/d for 28 days and 5 mg of medroxyprogesterone acetate during the last 14 days) or placebo (n = 12). Plasma samples were collected before and during treatment (days 0, 15, 43, 71). High-density lipoprotein (HDL) lipid content, lipoprotein (Lp)A-I and LpA-I:LpA-II concentration, lecithin:cholesterol acyl transferase activity (LCAT), phospholipid transfer protein (PLTP) activity, and the plasma capacity to carry out cholesterol efflux from Fu5AH cells were measured. Most significant changes were found within the first 15 days after HRT. After 71 days of HRT, we found an increase in LpA-I lipoparticles (27%) and the following HDL lipids: phospholipids (21%), triglycerides (45%), and free cholesterol (43%), as well as an increase in cholesterol efflux (12.5%). PLTP activity, on the other hand, decreased 21% after 71 days of treatment. No significant changes in LCAT activity, HDL-cholesterol ester or LpA-I:LpA-II particles were found. Positive correlation between cholesterol efflux and the variables LpA-I and HDL-phospholipids were observed. PLTP was negatively correlated with apolipoprotein (apo) A-I, LpA-I, and LpA-I:LpA-II. In summary, our study, performed during 3 hormonal cycles, shows that HRT not only modifies HDL-cholesterol level, but also its lipid composition and HDL lipoparticle distribution. HRT enhances the plasma capacity to carry out cholesterol efflux from the Fu5AH system and decreases the activity of PLTP, a key protein regulating HDL levels. Considering the protocol sampling, these results represent mainly the estrogenic effect of HRT.     

TNFalpha induces ABCA1 through NF-kappaB in macrophages and in phagocytes ingesting apoptotic cells

Recent evidence suggests that tumor necrosis factor alpha (TNFalpha) signaling in vascular cells can have antiatherogenic consequences, but the mechanisms are poorly understood. TNFalpha is released by free cholesterol-loaded apoptotic macrophages, and the clearance of these cells by phagocytic macrophages may help to limit plaque development. Macrophage cholesterol uptake induces ATP-binding cassette (ABC) transporter ABCA1 promoting cholesterol efflux to apolipoprotein A-I and reducing atherosclerosis. We show that TNFalpha induces ABCA1 mRNA and protein in control and cholesterol-loaded macrophages and enhances cholesterol efflux to apolipoprotein A-I. The induction of ABCA1 by TNFalpha is reduced by 65% in IkappaB kinase beta-deficient macrophages and by 30% in p38alpha-deficient macrophages, but not in jun kinase 1 (JNK1)- or JNK2-deficient macrophages. To evaluate the potential pathophysiological significance of these observations, we fed TNFalpha-secreting free cholesterol-loaded apoptotic macrophages to a healthy macrophage monolayer (phagocytes). ABCA1 mRNA and protein were markedly induced in the phagocytes, a response that was mediated both by TNFalpha signaling and by liver X receptor activation. Thus, TNFalpha signals primarily through NF-kappaB to induce ABCA1 expression in macrophages. In atherosclerotic plaques, this process may help phagocytic macrophages to efflux excess lipids derived from the ingestion of cholesterol-rich apoptotic corpses.     

Delayed loss of cholesterol from a localized lipoprotein depot in apolipoprotein A-I-deficient mice

The anti-atherogenic role of high density lipoprotein is well known even though the mechanism has not been established. In this study, we have used a novel model system to test whether removal of lipoprotein cholesterol from a localized depot will be affected by apolipoprotein A-I (apo A-I) deficiency. We compared the egress of cholesterol injected in the form of cationized low density lipoprotein into the rectus femoris muscle of apo A-I K-O and control mice. When the injected lipoprotein had been labeled with [³H]cholesterol, the t½ of labeled cholesterol loss from the muscle was about 4 days in controls and more than 7 days in apo A-I K-O mice. The loss of cholesterol mass had an initial slow (about 4 days) and a later more rapid component; after day 4, the disappearance curves for apo A-I K-O and controls began to diverge, and by day 7, the loss of injected cholesterol was significantly slower in apo A-I K-O than in controls. The injected lipoprotein cholesterol is about 70% in esterified form and undergoes hydrolysis, which by day 4 was similar in control and apo A-I K-O mice. The efflux potential of serum from control and apo A-I K-O mice was studied using media containing 2% native or delipidated serum. A significantly lower efflux of [³H]cholesterol from macrophages was found with native and delipidated serum from apo A-I K-O mice. In conclusion, these findings show that lack of apo A-I results in a delay in cholesterol loss from a localized depot in vivo and from macrophages in culture. These results provide support for the thesis that anti-atherogenicity of high density lipoprotein is related in part to its role in cholesterol removal.     

Interferon-gamma induces downregulation of Tangier disease gene (ATP-binding-cassette transporter 1) in macrophage-derived foam cells

Cholesterol efflux is a fundamental process that serves to mitigate cholesterol accumulation and macrophage foam cell formation. Recently, we reported that cholesterol efflux to high density lipoprotein subfraction 3 was reduced by interferon-gamma (IFN-gamma) and that this decrease was associated with an increase in acyl coenzyme A:cholesterol acyltransferase (ACAT) expression. In the present study, although treatment of murine peritoneal macrophages with IFN-gamma resulted in a 2-fold decrease in HDL-mediated cholesterol efflux, efflux to lipid-free apolipoprotein A-I was reduced >4-fold and approached basal levels. This decrease was associated with a 3- to 4-fold reduction in ATP-binding-cassette transporter 1 (ABC1) mRNA content, the gene responsible for the defect in Tangier disease. Consistent with the reduction in cholesterol and phospholipid efflux in Tangier fibroblasts, downregulation of ABC1 expression by IFN-gamma also resulted in reduced phosphatidylcholine and sphingomyelin efflux to apolipoprotein A-I. Whereas foam cells had a 3-fold increase in ABC1 mRNA, the decrease in ABC1 message levels by IFN-gamma was observed in foam cells and control macrophages. This effect of IFN-gamma was independent of general macrophage activation (inasmuch as similar changes were not detected with granulocyte-macrophage colony-stimulating factor) and was not observed with other ABC transporters (inasmuch as the expression of the transporter in antigen processing was upregulated 4-fold in these same cells). Therefore, by decreasing cholesterol efflux through pathways that include the upregulation of ACAT and the downregulation of ABC1, IFN-gamma can shift the equilibrium between macrophages and foam cells and thus impact the progression of an atherosclerotic lesion.     

High-density lipoprotein: Antioxidant and anti-inflammatory properties

The ability of high-density lipoprotein (HDL) to promote cholesterol efflux is an important component of its ability to protect against cardiovascular disease. In addition, the anti-inflammatory properties of HDL are important as well. As part of the innate immune system, HDL appears to have evolved to increase inflammation in the presence of an acute phase response but to inhibit inflammation in the absence of an acute phase response. In a study of humans with coronary heart disease, it was found that the patients who had proinflammatory HDL prior to statin therapy (and half of them despite a profound decrease in plasma lipids following statin therapy) continued to have proinflammatory HDL. Anti-inflammatory HDL was effective in promoting cholesterol efflux whereas proinflammatory HDL was relatively weak in its ability to promote cholesterol efflux. Oxidative alterations of the main protein of HDL, apolipoprotein A-I, impaired its capacity to promote cholesterol efflux from monocyte macrophages. Therefore, HDL composition, structure, and function appear to be more crucial than HDL cholesterol concentrations in determining risk for cardiovascular disorders.     

Opposite effects of plasma from human apolipoprotein A-II transgenic mice on cholesterol efflux from J774 macrophages and Fu5AH hepatoma cells

Overexpression of human apolipoprotein A-II (hapo A-II) in transgenic mice (hAIItg mice) induced marked hypertriglyceridemia and low levels of plasma high density lipoprotein (HDL) with a high hapo A-II content. We sought to determine whether cholesterol efflux to plasma and HDL from these mice would be affected. In the Fu5AH cell system, plasma from hAIItg mice induced a markedly lower cholesterol efflux than did control plasma, in accordance with the dependence of efflux on HDL concentration. Moreover, HDLs from hAIItg mice were less effective acceptors than were control HDLs. In the J774 macrophage cell system, pretreatment with cAMP, which upregulates ATP binding cassette transporter 1, induced a marked increase in the efflux to hAIItg plasma as well as to purified hapo A-I and hapo A-II, whereas it had no effect on cholesterol efflux to control plasma. A strong positive correlation was established between percent cAMP stimulation of efflux and plasma hapo A-II concentration. The cAMP stimulation of efflux to hAIItg mouse plasma may be linked to the presence of pre-beta migrating HDL containing hapo A-II. Thus, despite lower HDL and apolipoprotein A-I contents, the increased ability of plasma from hAIItg mice to extract cholesterol from macrophage-like cells may have an antiatherogenic influence.     

ABCA1促胆固醇流出防治动脉粥样硬化的机制及调控

动脉血管的炎症反应和胆固醇的积累是动脉粥样硬化形成的高危因素,因此抑制巨噬细胞炎症反应和促进胆固醇流出已成为治疗动脉粥样硬化的有效途径。三磷酸腺苷结合盒转运体A1（ATP binding cassette transporter A1,ABCA1）能将细胞内游离胆固醇转运给贫脂的载脂蛋白A-I,从而促进高密度脂蛋白的形成,介导胆固醇的流出。miRNA（microRNA,miRNA） 作为一种非编码的微小RNA,通过降解靶基因mRNA或阻碍其翻译,发挥ABCA1转录后的调控作用。因此探究ABCA1的作用机制及调控有利于动脉粥样硬化的有效防治。