RESUMEN

BACKGROUND: Cardiovascular diseases are one of the prime causes of mortality globally. Therefore, concerted efforts are made to prevent or manage disruptions from normal functioning of the cardiovascular system. Disruption in lipid metabolism is a major contributor to cardiovascular dysfunction. This review examines how lecithin impacts lipid metabolism and cardiovascular health. It emphasizes lecithin's ability to reduce excess low-density lipoproteins (LDL) while specifically promoting the synthesis of high-density lipoprotein (HDL) particles, thus contributing to clearer understanding of its role in cardiovascular well-being. Emphasizing the importance of lecithin cholesterol acyltransferase (LCAT) in the reverse cholesterol transport (RCT) process, the article delves into its contribution in removing surplus cholesterol from cells. This review aims to clarify existing literature on lipid metabolism, providing insights for targeted strategies in the prevention and management of atherosclerotic cardiovascular disease (ASCVD). This review summarizes the potential of lecithin in cardiovascular health and the role of LCAT in cholesterol metabolism modulation, based on articles from 2000 to 2023 sourced from databases like MEDLINE, PubMed and the Scientific Electronic Library Online. MAIN BODY: While studies suggest a positive correlation between increased LCAT activities, reduced LDL particle size and elevated serum levels of triglyceride-rich lipoprotein (TRL) markers in individuals at risk of ASCVD, the review acknowledges existing controversies. The precise nature of LCAT's potential adverse effects remains uncertain, with varying reports in the literature. Notably, gastrointestinal symptoms such as diarrhea and nausea have been sporadically documented. CONCLUSIONS: The review calls for a comprehensive investigation into the complexities of LCAT's impact on cardiovascular health, recognizing the need for a nuanced understanding of its potential drawbacks. Despite indications of potential benefits, conflicting findings warrant further research to clarify LCAT's role in atherosclerosis.

RESUMEN

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is an ultra-rare autosomal recessive disease characterized by very low high-density lipoprotein cholesterol (HDL-C) levels, corneal opacity, anemia, and progressive renal disease. The rate and severity of renal disease are variable across FLD patients and the biomarkers and risk factors for disease progression are poorly understood. Here we report a 30 year-long comparative analysis of the clinical and laboratory biomarkers in an FLD patient with accelerated renal decline, who underwent two kidney and one liver transplantations. Results show that elevated triglyceride and non-HDL-C levels may promote the formation of LpX and accelerate renal function decline, whereas markers of anemia may be early predictors. Conversely, corneal opacity progresses at a steady rate and does not correlate with lipid, hematologic, or renal biomarkers. Our study suggests that monitoring of markers of anemia may aid the early detection and timely management of kidney disease with conservative therapies. Furthermore, it suggests that controlling hypercholesterolemia and hypertriglyceridemia may help improve renal disease prognosis.

Asunto(s)

RESUMEN

The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors characterised by central obesity, atherogenic dyslipidaemia, and changes in the circulating lipidome; the underlying mechanisms that lead to this lipid remodelling have only been partially elucidated. This study used an integrated "omics" approach (untargeted whole serum lipidomics, targeted proteomics, and lipoprotein lipidomics) to study lipoprotein remodelling and HDL composition in subjects with central obesity diagnosed with MetS (vs. controls). Compared with healthy subjects, MetS patients showed higher free fatty acids, diglycerides, phosphatidylcholines, and triglycerides, particularly those enriched in products of de novo lipogenesis. On the other hand, the "lysophosphatidylcholines to phosphatidylcholines" and "cholesteryl ester to free cholesterol" ratios were reduced, pointing to a lower activity of lecithin cholesterol acyltransferase (LCAT) in MetS; LCAT activity (directly measured and predicted by lipidomic ratios) was positively correlated with high-density lipoprotein cholesterol (HDL-C) and negatively correlated with body mass index (BMI) and insulin resistance. Moreover, many phosphatidylcholines and sphingomyelins were significantly lower in the HDL of MetS patients and strongly correlated with BMI and clinical metabolic parameters. These results suggest that MetS is associated with an impairment of phospholipid metabolism in HDL, partially led by LCAT, and associated with obesity and underlying insulin resistance. This study proposes a candidate strategy to use integrated "omics" approaches to gain mechanistic insights into lipoprotein remodelling, thus deepening the knowledge regarding the molecular basis of the association between MetS and atherosclerosis.

Asunto(s)

RESUMEN

Recently we established a cell-free assay to evaluate "cholesterol uptake capacity (CUC)" as a novel concept for high-density lipoprotein (HDL) functionality and demonstrated the feasibility of CUC for coronary risk stratification, although its regulatory mechanism remains unclear. HDL fluidity affects cholesterol efflux, and trans fatty acids (TFA) reduce lipid membrane fluidity when incorporated into phospholipids (PL). This study aimed to clarify the effect of TFA in HDL-PL on CUC. Serum was collected from 264 patients after coronary angiography or percutaneous coronary intervention to measure CUC and elaidic acid levels in HDL-PL, and in vitro analysis using reconstituted HDL (rHDL) was used to determine the HDL-PL mechanism affecting CUC. CUC was positively associated with HDL-PL levels but negatively associated with the proportion of elaidic acid in HDL-PL (elaidic acid in HDL-PL/HDL-PL ratio). Increased elaidic acid-phosphatidylcholine (PC) content in rHDL exhibited no change in particle size or CUC compared to rHDL containing oleic acid in PC. Recombinant human lecithin-cholesterol acyltransferase (LCAT) enhanced CUC, and LCAT-dependent enhancement of CUC and LCAT-dependent cholesterol esterification were suppressed in rHDL containing elaidic acid in PC. Therefore, CUC is affected by HDL-PL concentration, HDL-PL acyl group composition, and LCAT-dependent cholesterol esterification. Elaidic acid precipitated an inhibition of cholesterol uptake and maturation of HDL; therefore, modulation of HDL-PL acyl groups could improve CUC.

Asunto(s)

RESUMEN

RATIONALE & OBJECTIVE: Lecithin-cholesterol acyltransferase (LCAT) catalyzes the maturation of high-density lipoprotein. Homozygosity for loss-of-function mutations causes familial LCAT deficiency (FLD), characterized by corneal opacities, anemia, and renal involvement. This study sought to characterize kidney biopsy findings and clinical outcomes in a family with FLD. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: 2 (related) index patients with clinically apparent FLD were initially identified. 110 of 122 family members who consented to genetic analysis were also studied. PREDICTORS: Demographic and laboratory parameters (including lipid profiles and LCAT activity) and full sequence analysis of the LCAT gene. Kidney histologic examination was performed with samples from 6 participants. OUTCOMES: Cardiovascular and renal events during a median follow-up of 12 years. Estimation of annual rate of decline in glomerular filtration rate. ANALYTICAL APPROACH: Analysis of variance, linear regression analysis, and Fine-Gray competing-risk survival analysis. RESULTS: 9 homozygous, 57 heterozygous, and 44 unaffected family members were identified. In all affected individuals, full sequence analysis of the LCAT gene revealed a mutation (c.820C>T) predicted to cause a proline to serine substitution at amino acid 274 (P274S). Homozygosity caused a complete loss of LCAT activity. Kidney biopsy findings demonstrated lipid deposition causing glomerular basement membrane thickening, mesangial expansion, and "foam-cell" infiltration of kidney tissue. Tubular atrophy, glomerular sclerosis, and complement fixation were associated with worse kidney outcomes. Estimated glomerular filtration rate deteriorated among homozygous family members at an average annual rate of 3.56 mL/min/1.73 m2. The incidence of cardiovascular and renal complications was higher among homozygous family members compared with heterozygous and unaffected members. Mild thrombocytopenia was a common finding among homozygous participants. LIMITATIONS: The presence of cardiovascular disease was mainly based on medical history. CONCLUSIONS: The P274S LCAT mutation was found to cause FLD with renal involvement. Tubular atrophy, glomerular sclerosis, and complement fixation were associated with a worse renal prognosis.

Asunto(s)

RESUMEN

BACKGROUND: Elevation of low-density lipoprotein (LDL) cholesterol is the hallmark of the dyslipidemia observed in hypothyroidism, but alterations on high-density lipoprotein (HDL) plasma levels and metabolism are less understood. The aim of this study was to explore aspects of HDL metabolism and enzymes that act on HDL after a short period of overt hypothyroidism. METHODS: Eighteen women (age 44 ± 11 years; body mass index 27.9 ± 5.2 kg/m2) were studied before total thyroidectomy for thyroid cancer, when they were euthyroid, and after thyroidectomy, in overt hypothyroidism for three weeks, following levothyroxine withdrawal for performance of a whole-body scan. RESULTS: Thyrotropin and free thyroxine confirmed hypothyroidism; low thyroglobulin and radioiodine uptake indicated near absence of thyroid tissue. LDL cholesterol (125 ± 35 vs. 167 ± 40 mg/dL; p = 0.0002), HDL cholesterol (HDL-C; 39 ± 8 vs. 46 ± 10 mg/dL; p = 0.0025), non-HDL-C (149 ± 38 vs. 201 ± 46 mg/dL; p < 0.0001), unesterified cholesterol (53 ± 10 vs. 70 ± 16 mg/dL; p = 0.0003), apolipoprotein (apo) A-I (1.32 ± 0.19 vs. 1.44 ± 0.22 g/L; p < 0.04), and apo B (0.97 ± 0.25 vs. 1.31 ± 0.28 g/L; p < 0.0001) plasma concentrations were all higher in hypothyroidism compared to values in the euthyroid state, but triglycerides and Lp(a) were unchanged. There were no changes in HDL particle size and lipid composition, cholesteryl ester transfer protein and lecithin cholesterol acyltransferase concentrations and in paraoxonase-1 activity. Regarding the in vitro assay to estimate lipid transfer to HDL, there were no changes when comparing the euthyroid to the hypothyroid state, but when adjusted for HDL-C, the unesterified cholesterol (0.14 ± 0.03 vs. 0.11 ± 0.02; p < 0.0001), triglycerides (0.11 ± 0.02 vs. 0.09 ± 0.02; p < 0.0001), phospholipids (0.44 ± 0.09 vs. 0.40 ± 0.07; p = 0.0205), and esterified cholesterol (0.14 ± 0.03 vs. 0.13 ± 0.03; p = 0.0043) transfer to HDL were all diminished in hypothyroidism. CONCLUSIONS: In short-term hypothyroidism, HDL-C increased, but this did not increase the capacity of the HDL fraction to receive lipids or the activity of paraoxonase-1, the anti-oxidation enzyme associated to HDL.

Asunto(s)

RESUMEN

INTRODUCTION: Lecithin cholesterol acyltransferase (LCAT) deficiency is an autosomal recessive disorder occurred by different mutations in the LCAT gene that cause two extremely rare syndromes including familial LCAT deficiency (FLD) and fish-eye disease (FED). Unlike FED in FLD renal failure is the most important defect due to deposition of abnormal lipoproteins in the renal stroma. In this study, FLD patients from the North of Iran were investigated for mutations in the LCAT gene. MATERIALS AND METHODS: Eight patients with corneal opacification and renal defect were analyzed for mutations in the LCAT gene by PCR sequencing. RESULTS: Sequencing analysis revealed a missense pathogenic variation c.301 G>A in exon 2 of LCAT gene in all patients changing the amino acid aspartate to asparagine at the conserved position of amino acid 101 of LCAT protein. CONCLUSION: In this study, a very rare variation was reported for the first time in this part of the world. Investigation of a larger number of LCAT patients in different parts of Iran can provide availability of mutations panel that is useful for phenotype prediction and also prenatal diagnosis programming in families with a previous history of the disease.

RESUMEN

AIMS: Reverse cholesterol transport (RCT) is a process that prevents atherosclerosis. Studies showed that exercise training for strengthening cardiac muscle, increasing heart lipid metabolism and its potency against risk factors could protect cardiovascular health. Thus, the present study aims to investigate the effects of high intensity interval training (HIIT) on RCT and its related elements in plasma and tissues (liver and intestine) of rats. MATERIALS AND METHODS: Twenty adult male Wistar rats were randomly divided into control (n = 10) and trained (n = 10) groups. The trained group undertook HIIT (90%-95% of VO2max, five days/week, for 10 weeks) on a treadmill. The rats were killed five days after the last training session to minimize the effects of the last training session. KEY FINDINGS: A higher and significant ABCA1 mRNA was observed in the liver and intestine of trained rats. However, ABCG1 and LXR expressions only increased in the liver following the HIIT. These changes in the expression of the trained rats were accompanied by higher changes in plasma LCAT and HDL levels. SIGNIFICANCE: The responses of ABCA1, as a key player in plasma HDL biogenesis, are similar in liver and intestine tissues after the HIIT program. However, different responses of ABCG1 and LXR in the liver and intestine tissues of the trained rats confirm the main role of the liver than the intestine in HDL biogenes. Therefore, HIIT modality result in cardiovascular protection by increasing the expression of genes involved in RCT and biogenesis of HDL.

Asunto(s)

RESUMEN

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a rare inherited disorder that causes an extremely low high-density lipoprotein cholesterol concentration in serum. Recently, acquired LCAT deficiency caused by IgG antibodies to LCAT, without any LCAT gene mutation, was reported. Here we describe a case of acquired LCAT deficiency occurring in association with sarcoidosis. The patient was a Japanese female aged 70 years, had no mutation in the LCAT gene exon sequence, but had an LCAT inhibitor factor in her serum, detected using lipoprotein-deficient serum. She was diagnosed with acquired LCAT deficiency. Her abnormalities of serum lipoproteins improved spontaneously during three and a half years. Because they require different treatment strategies, distinction between familial lecithin:cholesterol acyltransferase deficiency (FLD) and acquired LCAT deficiency by gene sequencing is warranted, especially in cases without corneal clouding.

RESUMEN

SCOPE: Consumption of olive oil (OO) phenolic compounds (PCs) has beneficial effects on lipid profile. HDL functionality is currently considered to be a more important issue than its circulating quantity. Our aim was to assess whether functional virgin olive oils (FVOOs), one enriched with its own PC (500 ppm; FVOO) and another with OOPC (250 ppm) plus additional complementary PCs from thyme (250 ppm) (total: 500 ppm; FVOOT (functional virgin olive oil with thyme)), could improve HDL functionality related properties versus a virgin OO control (80 ppm; VOO). METHODS AND RESULTS: In a randomized, double-blind, crossover, controlled trial, 33 hypercholesterolemic volunteers received 25 mL/day of VOO, FVOO, and FVOOT during 3 wk. HDL cholesterol increased 5.74% (p < 0.05) versus its baseline after the FVOOT consumption in the participants without hypolipidemic medication. We detected, after FVOOT consumption, an increase in HDL2 -subclass (34.45, SD = 6.38) versus VOO intake (32.73, SD = 6.71). An increment in esterified cholesterol/free cholesterol and phospholipids/free cholesterol in HDL was observed after FVOOT consumption (1.73, SD = 0.56; 5.44, SD = 1.39) compared with VOO intervention (1.53, SD = 0.35; 4.97, SD = 0.81) and FVOO intervention (1.50, SD = 0.33; 4.97, SD = 0.81). Accordingly, lecithin-cholesterol acyltransferase mass increased after FVOOT consumption (1228 µg/mL, SD = 130), compared with VOO consumption (1160 µg/mL, SD = 144). An improvement in HDL oxidative-status was reflected after FVOOT consumption versus its baseline, given an increment in the paraoxonase activity (118 × 10(3) U/L, SD = 24). CONCLUSION: FVOOT improves HDL-subclass distribution and composition, and metabolism/antioxidant enzyme activities. FVOOT could be a useful dietary tool in the management of high cardiovascular risk patients.

Asunto(s)

RESUMEN

BACKGROUND: Lecithin cholesterol acyltransferase (LCAT) is an important enzyme in cholesterol metabolism that is involved in the esterification of cholesterol. A lack of this enzyme results in deranged metabolic pathways that are not completely understood, resulting in abnormal deposition of lipids in several organs. Clinically, it manifests with proteinuria, dyslipidemia and corneal opacity with progressive chronic kidney disease resulting in end-stage renal disease. CASE PRESENTATION: We herein present a case of a 30-year-old male with proteinuria that was not responsive to empiric management with angiotensin-converting enzyme (ACE) inhibitors and oral steroids. Physical examination revealed corneal ring opacity involving both eyes. Urinalysis revealed an active sediment. The 24-h proteinuria was 3.55 grams. Family history was positive for renal disease and dyslipidemia. Viral serology for human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV) were negative. Serum complements were normal and anti-nuclear antibody (ANA) was negative. We elected for a renal biopsy that revealed characteristic features of LCAT deficiency. The diagnosis of LCAT deficiency was established with a combination of clinical and pathological findings. CONCLUSIONS: Currently renal prognosis is poor but conservative management with ACE inhibitors and lipid lowering therapy in addition to steroids has been shown to retard progression to end-stage renal disease. However newer therapies such as gene replacement and recombinant LCAT replacement are being studied with promising preliminary results.

RESUMEN

This study aims to evaluate the genetic basis and activity of lecithin cholesterol acyltransferase (LCAT) in a novel Mongolian gerbil model for hyperlipidemia. Gerbils may be susceptible to high fat and cholesterol (HF/HC) diets, which can rapidly lead to the development of hyperlipidemia. Approximately 10-30% of gerbils that are over 8months old and fed controlled diets spontaneously develop hyperlipidemia. Using the HF/HC diet model, we detected triglycerides (TG), total cholesterol (TC), HDL (high density lipoprotein)-C, LDL (low density lipoprotein)-C and LCAT in both old (>8months) and young gerbils. The TC and HDL-C levels were two times higher in old gerbils compared with young gerbils (P<0.01). However, in the old group the LCAT activity fell slightly compared with the normal lipidemia group. It is reasonable to hypothesize that this may be associated with single nucleotide polymorphisms of the LCAT gene. We cloned this gene to investigate the sensitivity of the gerbil to the HF/HC diet and spontaneous hyperlipidemia. The entire LCAT gene was cloned by splicing sequences of RACE (rapid amplification of cDNA ends) and nest-PCR products (AN: KC533867.1). The results showed that the 3683base pair gene consists of six exons and five introns. The LCAT protein consists of 444 amino acid (AA) residues, which are analogous to the human LCAT gene, and includes 24 signal peptide AA and 420 mature protein AA. Expression of LCAT was detected in the kidney, spleen and adrenal tissue, apart from the liver, by immunohistochemistry. The abundance of the protein was greater in the older group compared with the control group. Polymorphisms were analyzed by PCR-SSCP (PCR-single-strand conformation polymorphism) but none were found in 444 animals of the ZCLA closed population (a Chinese cultured laboratory gerbil population).

Asunto(s)