Academic literature on the topic 'Lipoproteins – Metabolism – Disorders'

Subclinical hypothyroidism is common in general practice. The clinical significance of latent thyroid dysfunction has not yet been determined. The parameters of lipid metabolism and oxidative stress were studied in patients suffering from subclinical hypothyroidism between the ages of 18 and 50 years. They had a level of thyroid stimulating hormone ≥4 mIU/l, the level of free thyroxine was normal. The control group consisted of healthy individuals with thyroid-stimulating hormone level of 0,4-2,4 mIU/l. Thyroid status, thyroid peroxidase antibodies, lipid profile, malondialdehyde-modified low-density oxidized lipoproteins, antibodies to low-density oxidized lipoproteins, homocysteine were determined for all individuals. With the repeated determination of thyroid-stimulating hormone in 16,8% patients spontaneous recovery of thyroid-stimulating blood hormone level was observed, which was associated with lower values of thyroid-stimulating hormone and the absence of thyroid peroxidase antibodies. In the group of patients with thyroid stimulating hormone levels ≥7 mIU/l, the total cholesterol level was significantly (p=0,02) higher than in the control group. In patients with elevated values of malondialdehyde-modified oxidized low-density lipoprotein, thyroid stimulating hormone level of ≥7 mIU/l was more frequently detected. A negative correlation was found between the level of IgG antibodies to low-density oxidized lipoproteins and the concentration of free thyroxin. In the control group, the correlation was found between the concentration of IgG antibodies to low-density oxidized lipoproteins and the level of thyroid-stimulating hormone. In the group of subclinical hypothyroidism, the concentration of homocysteine was significantly (p=0,01) higher in men. In patients with subclinical hypothyroidism, more often hyperhomocysteinemia was detected compared with the control group. The results suggest that subclinical hypothyroidism is associated with initial changes in the metabolism of lipids and homocysteine.

Aim. The number of patients with endocrine disorders in the world, in particular, Graves’ disease is continuously increasing. Recent studies have determined the fact of insulin resistance in thyroid disorders. On the one hand, numerous researches prove correlation of hypothyroidism with arterial hypertension, ischaemic heart disease and lipid metabolism disorder, on the other – carbohydrate metabolism disorder and hyper-sympathicotonia are closely associated with hyperthyroidism. The subject of the research was to study the correlation of insulin resistance, lipid and carbohydrate metabolism indices in patients with Graves’disease. Material and Methods. During the study 53 (37 female and 16 male) patients with Graves’ disease with noticed IR have been examined. At the beginning, after 3– and 6-months thyreostatic therapy with insulin sensitizers (metformin or pioglitazone) the following investigations have been performed: assessing thyroid-stimulating hormone levels, free thyroxine and triiodothyronine; assessing glycated haemoglobin, glucose, C-peptide and fasting insulin as primary IR markers; calculating НОМА-IR index for analysing tissue sensitivity to insulin; calculating НОМА-β index for evaluating the functional capacity of β-cells of islets of Langerhans; measuring Caro indices to monitor hyperinsulinemia, measuring total cholesterol level, low-density lipoproteins, very-low-density lipoproteins, high-density lipoproteins , triglycerides, for analysing IR in relation to lipid metabolism. Results. The research results found out that free thyroid hormones and thyroid-stimulating hormone are closely related to lipid metabolism. Thus, thyroid-stimulating hormone was characterized as having direct correlation with low-density lipoproteins, while the free thyroxine inversely correlated with total cholesterol, low-density lipoproteins, and high-density lipoproteins. The free triiodothyronine negatively correlated with high-density lipoproteins. The research has also determined the direct correlation between insulin and free thyroxine, as well as free triiodothyronine in patients with diffuse toxic goitre. Conclusions. The study proves the presence of insulin resistance in patients with Graves’ disease that generates interest to further study of the changes in insulin sensitivity, relation of insulin resistance to thyroid-stimulating hormone, thyroid hormones and looking for the ways to correct these disorders.

Disorders of lipid metabolism in endocrine diseases are a frequent occurrence in the daily practice of a doctor and usually have secondary nature. In thyrotoxicosis they have normal or decreased level of total cholesterol and low-density lipoproteins. A clinical case of a patient with thyrotoxicosis, hypercholesterolemia and hypertriglyceridemia is presented. The clinical and laboratory results of the study of the child and his parents are presented. DNA testing was conducted to clarify the diagnosis and conduct differential diagnosis of dyslipidemia type. This case shows difficulties in the diagnostic search for the etiology of dyslipidemia and its correction.

Dysregulation of glucose and lipid metabolism increases plasma levels of lipoproteins and triglycerides, resulting in vascular endothelial damage. Remarkably, the oxidation of lipid and lipoprotein particles generates electronegative lipoproteins that mediate cellular deterioration of atherosclerosis. In this review, we examined the core of atherosclerotic plaque, which is enriched by byproducts of lipid metabolism and lipoproteins, such as oxidized low-density lipoproteins (oxLDL) and electronegative subfraction of LDL (LDL(−)). We also summarized the chemical properties, receptors, and molecular mechanisms of LDL(−). In combination with other well-known markers of inflammation, namely metabolic diseases, we concluded that LDL(−) can be used as a novel prognostic tool for these lipid disorders. In addition, through understanding the underlying pathophysiological molecular routes for endothelial dysfunction and inflammation, we may reassess current therapeutics and might gain a new direction to treat atherosclerotic cardiovascular diseases, mainly targeting LDL(−) clearance.

Chronic renal failure (CRF) results in profound lipid disorders, which stem largely from dysregulation of high-density lipoprotein (HDL) and triglyceride-rich lipoprotein metabolism. Specifically, maturation of HDL is impaired and its composition is altered in CRF. In addition, clearance of triglyceride-rich lipoproteins and their atherogenic remnants is impaired, their composition is altered, and their plasma concentrations are elevated in CRF. Impaired maturation of HDL in CRF is primarily due to downregulation of lecithin-cholesterol acyltransferase (LCAT) and, to a lesser extent, increased plasma cholesteryl ester transfer protein (CETP). Triglyceride enrichment of HDL in CRF is primarily due to hepatic lipase deficiency and elevated CETP activity. The CRF-induced hypertriglyceridemia, abnormal composition, and impaired clearance of triglyceride-rich lipoproteins and their remnants are primarily due to downregulation of lipoprotein lipase, hepatic lipase, and the very-low-density lipoprotein receptor, as well as, upregulation of hepatic acyl-CoA cholesterol acyltransferase (ACAT). In addition, impaired HDL metabolism contributes to the disturbances of triglyceride-rich lipoprotein metabolism. These abnormalities are compounded by downregulation of apolipoproteins apoA-I, apoA-II, and apoC-II in CRF. Together, these abnormalities may contribute to the risk of arteriosclerotic cardiovascular disease and may adversely affect progression of renal disease and energy metabolism in CRF.

Menopause is clinically diagnosed as a condition when a woman has not menstruated for one year. During the menopausal transition period, there is an emergence of various lipid metabolic disorders due to hormonal changes, such as decreased levels of estrogens and increased levels of circulating androgens; these may lead to the development of metabolic syndromes including cardiovascular diseases and type 2 diabetes. Dysregulation of lipid metabolism affects the body fat mass, fat-free mass, fatty acid metabolism, and various aspects of energy metabolism, such as basal metabolic ratio, adiposity, and obesity. Moreover, menopause is also associated with alterations in the levels of various lipids circulating in the blood, such as lipoproteins, apolipoproteins, low-density lipoproteins (LDLs), high-density lipoproteins (HDL) and triacylglycerol (TG). Alterations in lipid metabolism and excessive adipose tissue play a key role in the synthesis of excess fatty acids, adipocytokines, proinflammatory cytokines, and reactive oxygen species, which cause lipid peroxidation and result in the development of insulin resistance, abdominal adiposity, and dyslipidemia. This review discusses dietary recommendations and beneficial compounds, such as vitamin D, omega-3 fatty acids, antioxidants, phytochemicals—and their food sources—to aid the management of abnormal lipid metabolism in postmenopausal women.

The liver and intestine have complementary and coordinated roles in lipoprotein metabolism. Despite their highly specialized functions, assembly and secretion of triglyceride-rich lipoproteins (TRL; apoB-100-containing VLDL in the liver and apoB-48-containing chylomicrons in the intestine) are regulated by many of the same hormonal, inflammatory, nutritional, and metabolic factors. Furthermore, lipoprotein metabolism in these two organs may be affected in a similar fashion by certain disorders. In insulin resistance, for example, overproduction of TRL by both liver and intestine is a prominent component of and underlies other features of a complex dyslipidemia and increased risk of atherosclerosis. The intestine is gaining increasing recognition for its importance in affecting whole body lipid homeostasis, in part through its interaction with the liver. This review aims to integrate recent advances in our understanding of these processes and attempts to provide insight into the factors that coordinate lipid homeostasis in these two organs in health and disease.

The review describes a number of competing views on the main causes of cholesterol accumulation in atherosclerotic vessels. On the one hand, unregulated cholesterol influx into arterial intima is primarily related to the increasing proportion of atherogenic lipoproteins in the lipoprotein spectrum of blood. On the other hand, the leading role in this process is assigned to the increased permeability of endothelium for atherogenic lipoproteins. The increased ability of arterial intima connective tissue to bind atherogenic blood lipoproteins is also considered to be the leading cause of cholesterol accumulation in the vascular wall. The key role in cholesterol accumulation is also assigned to unregulated (by a negative feedback mechanism) absorption of atherogenic lipoproteins by foam cells. It is suggested that the main cause of abundant cholesterol accumulation in atherosclerotic vessels is significant inflow of this lipid into the vascular wall during vasa vasorum hemorrhages.The article also provides arguments, according to which disorder of fatty acid metabolism in arterial wall cells can initiate accumulation of neutral lipids in them, contribute to the inflammation and negatively affect the mechanical conditions around the vasa vasorum in the arterial walls. As a result, the impact of pulse waves on the luminal surface of the arteries will lead to frequent hemorrhages of these microvessels. At the same time, adaptive-muscular intima hyperplasia, which develops in arterial channel areas subjected to high hemodynamic loads, causes local hypoxia in a vascular wall. As a result, arterial wall cells undergo even more severe lipid transformation. Hypoxia also stimulates vascularization of the arterial wall, which contributes to hemorrhages in it. With hemorrhages, free erythrocyte cholesterol penetrates into the forming atherosclerotic plaque, a part of this cholesterol forms cholesterol esters inside the arterial cells. The saturation of erythrocyte membranes with this lipid in conditions of hypercholesterolemia and atherogenic dyslipoproteinemia contributes to the process of cholesterol accumulation in arteries.

Objective of this study was to determine the characteristics of the metabolic disorders of lipids and lipoproteins (LP) in the blood in 112 patients with systemic rheumatic diseases.Material and methods. In all patients, the level of C-reactive protein (CRP), the content of malonic aldehyde (MA) in circulating monocytes, in blood plasma, and catalase activity were determined. The presence and severity of pro-atherogenic status were evaluated by the content of modified low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL) in the blood, which was determined by the bioassay method using peritoneal mouse macrophages. The immunogenicity of modified LР was determined by the content in the circulating immune complexes (CIC) of cholesterol (Сhol) and triglycerides (TG). The spectrum of lipids and LP in the blood was evaluated in detail with an additional determination of the plasma level of proteins apoB and apoA-1 were determined.Results. The obtained results show the existence in the examined patients of significant systemic inflammation in conjunction with the distinct proatherogenic metabolic state that was revealed by lipoprotein modification with the appearance in them of auto-antigenic properties. These changes appeared despite the absence of significant traditional atherogenic risk factors. The results of the paired correlative analysis showed the existence of strong dependence between indexes of systemic inflammation, proatherogenic and immunogenic lipoprotein modification. Conclusions. When determining proatherogenic disorders of lipid and blood lipoproteins metabolism in patients with systemic rheumatic diseases, it is necessary to focus not on traditional risk factors, which may remain within normal values, but on the content of apoA-1, apoB proteins, their ratio, and the determination of modified lipoproteins blood and the severity of the autoimmune reaction to them.

The content of triglycerides in lipoprotein fraction of high density in patients with chronic calculus-free cholecystitis is studied. It is established that the li poprotein fraction is enriched by triglycerides, that it is modified and changes its functions. The lipid status disorders are found in all patients. In the Chazov and Klimov (1980) phenotyping the lipoprotein metabolism disorder is largely revealed by the IV type, their minimum degree by the IIA type.

Primary hyperparathyroidism (pHPT), characterized by elevated serum levels of calcium and parathyroid hormone (PTH), is associated with a number of metabolic derangements causing secondary manifestations. These include osteoporosis and increased risk of fractures, but also risk factors for cardiovascular morbidity and mortality. These risk factors include impaired glucose tolerance (IGT), dyslipidemia, increased body mass index and hypertension. While the skeletal abnormalities are mainly due to elevated PTH, the latter disturbances are still unexplained. Non-insulin dependent diabetes mellitus (NIDDM), IGT, dyslipidemia and hypertension are all included in the metabolic syndrome, also associated with morbidity and mortality in cardiovascular diseases.

In this thesis, decreased bone mineral density (BMD) and variables of the metabolic syndrome are explored in patients with mild and normocalcemic pHPT before and after parathyroidectomy. To further investigate the relationship between insulin sensitivity and calcium, a community-based cohort was investigated.

In two different patient cohorts of pHPT, lipoprotein alterations with decreased levels of HDL-cholesterol and elevated triglycerides were found in association with a high frequency of IGT, NIDDM and decreased insulin sensitivity. Parathyroidectomy had effects on the dyslipidemia and in part on the glucose metabolism. The disturbed glucose metabolism in pHPT was substantiated by results from the general population by a negative association between insulin sensitivity, measured by hyperinsulinemic clamp, and serum calcium.

In conclusion, normocalcemic, mild and overt pHPT are associated with a range of risk factors for cardiovascular diseases, development of NIDDM and decreased BMD in cortical as well as trabecular bone. These findings explain, at least in part, the elevated morbidity and mortality from cardiovascular disease as well as fractures, reported in pHPT patients. Moreover, in the general population, serum calcium is associated with decreased insulin sensitivity. Parathyroidectomy has positive effects on several, but not all, of the investigated metabolic parameters.

[Formulae and special characters can only be approximated here. Please see the pdf version of the abstract for an accurate reproduction.] Atherosclerosis is a common degenerative disease in which the clinical manifestations are often through stroke or myocardial infarction. Some of the established risk factors for atherosclerosis include elevated plasma low-density lipoprotein (LDL)-cholesterol levels, obesity, diabetes mellitus (DM) and cigarette smoking. Of the risk factors, an elevation in plasma LDL is one of the most established and the most researched. This is partly a consequence of the deposition of cholesterol within arterial intima being a crucial step in the progression of atherosclerosis, combined with the finding that LDL particles are a major transporter of cholesterol in circulation. Recently there is increasing evidence showing a role of the other major transporter of cholesterol in circulation, chylomicron remnants, in the progression of atherosclerosis. The notion of atherosclerosis as a postprandial phenomenon has been further substantiated by the emergence of evidence showing a direct role of chylomicron remnants in arterial cholesterol deposition. Based on evidence that chylomicron remnants are proatherogenic, the suggestion arises that accumulation of postprandial lipoproteins in plasma may add another dimension of risk to the development of coronary artery disease (CAD). This thesis tests the general hypothesis that individuals with or at high risk of CAD have postprandial dyslipidaemia and that this metabolic abnormality is correctable with a class of lipid-lowering drugs called statins. To test the hypothesis, clinical studies were conducted in normolipidaemic CAD patients, heterozygous familial hypercholesterolaemia (FH) and postmenopausal women with type 2 DM. Determination of postprandial dyslipidaemia by comparison with control populations were conducted initially in each patient group (Studies 1, 3 and 5), followed by intervention studies investigating possible modulation of the dyslipidaemia with a statin (Studies 2, 4 and 6). Six observation statements based on case-control comparisons of postprandial lipaemia in patients with or at risk of CAD and the effects of statins on postprandial dyslipidaemia in the patient groups were derived from the general hypothesis. The observation statements were examined in the individual studies described below. Postprandial lipoprotein metabolism was assessed using a number of methods. For comparison of postprandial lipaemia in Studies 1 and 2, a classic oral fat challenge was utilised. As markers of chylomicrons and chylomicron remnants, retinyl palmitate and triglyceride were measured postprandially as well as apolipoprotein (apo) B48 concentrations, a specific marker of intestinal lipoproteins. ApoB48 was also measured in the fasting state and found to predict the postprandial responses of retinyl palmitate, triglyceride and apoB48. This suggested that fasting measurement of apoB48 could be used as a simple indicator of postprandial dyslipidaemia. Consequently for Studies 3 - 6, fasting apoB48 measurements were used as primary markers of postprandial dyslipidaemia. Other markers for chylomicrons and their remnants utilised were fasting plasma concentrations of remnant-like particle-cholesterol (RLP-C) and apoC-III. As well as these static markers, chylomicron remnant catabolism was measured using a stable isotope breath test. The breath test involves the intravenous injection of a chylomicron remnant-like emulsion labelled with ¹³C-oleate and measurement of enriched ¹³CO2 in expired breath by isotope ratio mass spectrometry. The fractional catabolic rate (FCR) of the injected emulsion was subsequently calculated using multi-compartmental modeling (SAAM II). The studies are presented in this thesis as published and unpublished works. In Study 1, postprandial lipoprotein metabolism was compared between 18 normolipidaemic CAD patients (cholesterol 4.54 ± 0.12 mmol/L, triglyceride 1.09 ± 0.16) with 13 asymptomatic healthy controls using an oral fat challenge. Normolipidaemic CAD patients had higher postprandial area-under-curve (AUC) for triglyceride (+34%, p=0.019), retinyl palmitate (+74%, p=0.032) and apoB48 (+36%, p<0.001). Fasting apoB48 was also higher (+41%, p=0.001) and found to correlate significantly with AUC of triglyceride (p=0.017), retinyl palmitate (p=0.001) and apoB48 (p<0.001). The data suggest that normolipidaemic CAD patients have increased concentrations of intestinal lipoproteins in the fasting and postprandial state. In addition to these findings, significant correlations of fasting apoB48 with postprandial markers (p<0.02) suggests the fasting marker to be a simpler surrogate marker for the degree of total postprandial lipaemia. Study 2 investigated the effect of atorvastatin treatment on postprandial dyslipidaemia found in the 18 near-normolipidaemic CAD patients from Study 1. The trial was conducted in a randomised, placebo-controlled design, using oral fat challenges before and after 12-weeks atorvastatin/placebo treatment. Compared with the placebo group, atorvastatin decreased the total postprandial AUC for iii triglyceride (-22%, p=0.05) and apoB48 (-34%, p=0.013). Fasting markers of apoB48 (-35%, p=0.019) and RLP-C (-36%, p=0.032) also decreased significantly. Atorvastatin was also found to increase LDL-receptor activity by +218% (p<0.001) as reflected in binding studies. The data suggest atorvastatin reduces the fasting levels of intestinal lipoproteins as well as total postprandial lipaemia, but without acute dynamic changes in postprandial lipaemia. The reduction in fasting and total postprandial lipoprotein levels could be partly attributed to an increase in LDL-receptor mediated removal from circulation. In Study 3, postprandial lipaemia was compared in 15 heterozygous FH patients with 15 healthy controls. FH patients had higher fasting concentrations of apoB48 (+56%, p<0.001) and RLP-C (+48%, p=0.003). The elevation in these fasting markers of chylomicrons and their remnants suggests FH patients have postprandial dyslipidaemia due to an accumulation of these particles in plasma. Study 4 examined the effects of long- (> 6 months) and short-term (4 weeks) simvastatin treatment on modulating postprandial dyslipidaemia found in the 15 FH patients from Study 3. Short- and long-term simvastatin treatment decreased the fasting concentrations of apoB48 (-29% and 15% respectively, p<0.05) and RLP-C (both -38%, p<0.001), but did not significantly alter the FCR of the injected chylomicron remnant-like emulsion. The data suggest that in heterozygous FH both long- and short-term simvastatin treatments decrease the fasting markers of postprandial lipoproteins by mechanisms that may not be mediated via processes differentiated by the 13CO2 breath test. This implies that the effect on postprandial lipaemia may be from a decrease in production and/or a possible increase in catabolism of triglyceride-rich lipoproteins (TRLs). In Study 5, postprandial lipaemia was compared in 24 postmenopausal women age and body mass index matched with 14 postmenopausal women with type 2 DM. Postmenopausal diabetic women were found to have higher fasting concentrations of apoB48 (+21%, p=0.021) and apoC-III (+16%, p=0.042) as well as lower FCR of the chylomicron remnant-like emulsion (-50%, p<0.001). The data suggest that postmenopausal diabetic women have postprandial dyslipidaemia, and that this is due to delayed catabolism of chylomicron remnants. Study 6 was an hypothesis-generating exercise examining the effects of 4-weeks pravastatin treatment on postprandial dyslipidaemia found in 7 postmenopausal women with type 2 DM from Study 5. Although plasma LDL-cholesterol was reduced (-19%, p=0.028), there were no significant effects found on fasting apoB48 concentrations (-12%, p=0.116) or the FCR of the chylomicron remnant-like emulsion (+38%, p=0.345). A larger sample size of patients and/or treatment with a more potent statin at a dosage known to affect chylomicron remnant metabolism would be required to demonstrate a significant reduction in postprandial dyslipidaemia in postmenopausal women with type 2 DM. The results of the above mentioned studies combined support the general hypothesis that postprandial dyslipidaemia is a feature of patients with or at risk of CAD. This defect may be demonstrated using fasting apoB48 as an indicator of the degree of postprandial lipaemia. Postprandial dyslipidaemia may reflect a reduction in catabolism, as suggested with the breath test in type 2 DM, and/or an over overproduction of chylomicrons. Both these mechanisms would also increase competition for lipolysis and clearance pathways between hepatically and intestinally-derived lipoproteins. The exact mechanisms by which postprandial dyslipidaemia occurs are yet to be determined. Statins appear to improve defective postprandial lipaemia in patients with or at risk of CAD, which is in agreement with the general hypothesis. The effectiveness of a statin is dependant on their potency in inhibiting cholesterol biosynthesis and increasing receptor mediated clearance of LDL and chylomicron remnants. The studies conducted in this thesis show that postprandial dyslipidaemia can be reduced by statins but not to the extent demonstrated in controls. However, the demonstrated reduction in fasting and total postprandial lipaemia translates to a lowering in overall arterial exposure to circulating proatherogenic particles. The elevation in fasting and postprandial levels of proatherogenic chylomicron remnants found in the patient groups described in this thesis indicates another dimension to their risk of coronary disease. The reductions in the overall levels of proatherogenic particles in patients with or at high CAD risk, infers a possible reduction in the risk of coronary disease in these patients.

In order to examine the role of HDL in the control of lipoprotein metabolism, the levels of HDL subspecies, other lipoproteins, apolipoproteins and fatty acids were measured in four groups of subjects presenting clinical disorders which were possibly related to their lipid profiles. (1) A monoclonal antibody was raised against apolipoprotein A-I allowing the development of an ELISA. (2) In a comparison of 43 angina patients and 61 healthy control subjects, the levels of HDL₂, HDL_2b and HDL_2a were lower in the angina group and this was compensated for by an increase in levels of HDL_3b and HDL_3c. Plasma triglyceride and VLDL-cholesterol concentrations were higher in the angina group possibly giving rise to the low levels of HDL₂ subspecies by their effect on HDL particle conversion. The subspecies HDL_2b has been implicated in reverse cholesterol transport. (3) In a study of nine hypertriglyceridaemic subjects and 23 healthy controls there was a lower concentration of HDL_2b, HDL_2a and LDL-cholesterol and a higher concentration of HDL_3b and VLDL-cholesterol in the hypertriglyceridaemic group. This was possibly indicative of reduced LPL activity. The resulting high levels of plasma triglyceride are known to favour the conversion of HDL₂ to HDL₃. These results suggest that hypertriglyceridaemic patients have a reduced ability to eliminate surplus cholesterol by reverse cholesterol transport and would therefore be at increased risk of atherosclerosis. (4) In a study of 17 violent offenders and 25 control subjects, the HDL subfraction HDL_3a was higher in the offenders. The levels of the apolipoproteins E and A-IV were higher in the offender group perhaps having a role in the repair of damaged nervous tissue.