Post-menopausal hormone replacement therapy, coronary heart disease and plasma lipoproteins

At least 20 million postmenopausal women worldwide now use some form of hormone replacement therapy. This figure is increasing because the resistance of the medical community to these therapies is diminishing and because of increasing acknowledgement of the benefits of such therapies on the cardiovascular system. This is a remarkable development for a medication originally used to relieve menopausal symptoms such as hot flushes and to prevent bone loss. Although several mechanisms are now accepted to be involved in this protection from cardiovascular disease, changes in plasma lipoproteins remain a major area of research interest. The main issue in this field, whether the addition of a progestogen to postmenopausal oestrogen ('combined therapy') will diminish the benefits on the cardiovascular system, remains unresolved, but combined therapies have now been formulated that minimize the potentially detrimental effects of progestogens on plasma lipoproteins. Recent findings of interest include the effects of these therapies on plasma lipoprotein (a) concentration and on LDL particle size. Studies of the mechanisms behind such changes are needed.     

Composition and physical structure of atherogenic lipoproteins in ischemic heart disease

The results of comparative studies in atherogenic lipoproteins of blood plasma under heart ischemic disease (HID) which is accompanied by hypercholesterinemia or proceeds without disturbances in the lipid metabolism, evidence for considerable differences in the composition and physical structure of very low-density lipoproteins (VIDL) and low-density ones (LDP) under the investigated states. The decrease in the surface charge density and in sizes of VLDL, as compared to normal, which are least expressed at HID and an increase in the surface charge density with certain increase of LDL radii under this pathologic state are revealed.     

Peroxide modification of low density lipoproteins in ischemic heart disease

It is shown that the LDL peroxide lipid products level is 1.6-4 times higher in patients with the ischemic heart diseases (IHD) than in normal subjects. At the same time the LDL uptake by macrophages was identical in case of normal subjects and of IHD patients. It is suggested that the LDL premodification in the blood flow in the IHD patients promotes the further modification of LDL particles after their penetration into the vessel wall.     

Thermotropic structural rearrangements in blood plasma lipoproteins in ischemic heart disease

Structural properties of blood plasma lipoproteins (LP) from coronary heart disease (CHD) patients were examined. Substantial differences were found in the pattern of the heat-induced structural restitution of LP of all classes in health and disease. At the same time no such differences were discovered in lipids isolated from LP. In high density lipoproteins from the plasma of CHD patients, a decrease in the microenvironmental polarity was shown to take place at a depth of 8 A from the surface of LP. The data obtained indicate substantial changes in the structural organization of LP of all classes in CHD. It is assumed that these changes are consequent on the modification of apoproteins and/or protein-lipid interactions in LP.     

Obesity, adiponectin and vascular inflammatory disease

PURPOSE OF REVIEW: Obesity is the most common risk factor for cardiovascular diseases in industrial countries. It is now clear that adipose tissue secretes various bioactive substances, conceptualized as adipocytokines, and that dysregulation of adipocytokines directly contributes to obesity-related diseases. Chronic inflammatory processes contribute to the development of atherosclerosis. In this review, the authors focus on the relationship between adiponectin, a recently discovered anti-atherogenic adipocytokine, and vascular inflammation. RECENT FINDINGS: Plasma concentrations of adiponectin, an adipocyte-specific protein, are reduced in obese subjects and in patients with type 2 diabetes and coronary artery disease. Adiponectin inhibits the expression of tumor necrosis factor-alpha-induced endothelial adhesion molecules, macrophage-to-foam cell transformation, tumor necrosis factor-alpha expression in macrophages and adipose tissues, and smooth muscle cell proliferation. In addition, adenovirus-expressed adiponectin reduces atherosclerotic lesions in a mouse model of atherosclerosis, and adiponectin-deficient mice exhibit an excessive vascular remodeling response to injury. Clinically, hypoadiponectinemia is closely associated with increased levels of inflammatory markers such as C-reactive protein and interleukin-6. SUMMARY: Adiponectin acts as an anti-inflammatory and anti-atherogenic plasma protein. Adiponectin is an endogenous biologically relevant modulator of vascular remodeling linking obesity and vascular disease.     

Properties of plasma low density lipoproteins in patients with hypertriglyceridemia and ischemic heart disease

It has been shown that low-density plasma lipoproteins in patients with ischemic heart disease and hypertriglyceridemia are heavier in density, smaller in size, more negatively charged and more inclined to peroxide modification and aggregation than in healthy persons. The protein in the composition of such lipoproteins deviates towards the water phase, which may result in the masking of the domen, recognized by the BE-receptor and may lead to hyperlipidemia of a retaining character.     

Genetic polymorphisms, lipoproteins and coronary artery disease risk

Association studies between gene variants (polymorphisms) and measured intermediate phenotypes, such as lipid/lipoprotein levels, or disease endpoints such as coronary artery disease, are commonplace in the literature. But have we learnt anything from the shortcomings in study design and analytical strategies that have resulted in much controversy in this field over the last few years? This review highlights some of these problems. Using the lipoprotein lipase gene as an example, we evaluate new approaches to identifying polymorphisms that will stand up to linkage disequilibrium/association studies with complex disorders in this post Human Genome Project age, and emphasize the importance of gene-environment interaction in assessing the impact of gene variants.     

Obesity and cardiovascular disease

Available evidence clearly indicates a rapid progression in the prevalence of obesity worldwide. As a consequence, there has also been a marked increase in the prevalence of type 2 diabetes all over the world and this chronic metabolic disease is now considered as a coronary heart disease risk equivalent. However, even in the absence of the hyperglycaemic state which characterizes type 2 diabetic patients, non diabetic individuals with a specific form of obesity, named abdominal obesity, often show clustering metabolic abnormalities which include high triglyceride levels, increased apolipoprotein B, small dense low density lipoproteins and decreased high density lipoproteins-cholesterol levels, a hyperinsulinemic-insulin resistant state, alterations in coagulation factors as well as an inflammatory profile. This agglomeration of abnormalities has been referred to as the metabolic syndrome which can be identified by the presence of three of the five following variables: abdominal obesity, elevated triglyceride concentrations, low HDL-cholesterol levels, increased blood pressure and elevated fasting glucose. Post-mortem analyses of coronary arteries have indicated that obesity (associated with a high accumulation of abdominal fat measured at autopsy) was predictive of earlier and greater extent of large vessels atherosclerosis as well as increase of coronary fatty streaks. Metabolic syndrome linked to abdominal obesity is also predictive of recurrent coronary events both in post-myocardial infarction patients and among coronary artery disease men who underwent a revascularization procedures. It is suggested that until the epidemic progression of obesity is stopped and obesity prevented or at least properly managed, cardiologists will be confronted to an evolving contribution of risk factors where smoking, hypercholesterolemia and hypertension may be relatively less prevalent but at the expense of a much greater contribution of abdominal obesity and related features of the metabolic syndrome.     

Changes in the surface potential of plasma lipoproteins in ischemic heart disease. Studied with spin probes

Changes in lipoprotein surface potentials were studied by a positively charged analog as a spin probe. Low density lipoproteins (LDL) and high density lipoproteins (subfractions HDL2 and HDL3) of patients with coronary heart disease (CHD) were studied. CHD patients have revealed a significant decrease (by 14.4 +/- 0.3 mV) in LDL and an increase (by 6.3 +/- 2.0 mV) in HDL3 negative surface potential, as compared to the control. The increase in HDL2 surface potential in CHD patients was insignificant (1.9 +/- +/- 2.5 mV). The possible role of LDL and HDL3 surface potential changes in the mechanism of interaction of these types of lipoproteins with vascular wall and blood cellular membranes and in pathogenesis of CHD and atherosclerosis is discussed.