Cardiovascular disease lipid metabolism

Maturity-onset diabetes (now more frequently termed Type II or non-insulin-dependent diabetes mellitus, NIDDM) is associated with obesity, hyperlipoproteinaemia and an increased risk of cardiovascular disease. Lipid metabolism tends to be enhanced and an important characteristic is... 

TNF is a pleiotropic cytokine exerting a wide range of cellular responses, that affect biological processes such as lipid metabolism, coagulation, and insulin resistance and the function of endothelial cells. As a major proinflammatory cytokine TNF is also involved in progression of diseases like cancer, Alzheimer, Diabetes type II, cardiovascular, pulmonary or neurological disorders, and many autoimmune diseases. Blocking the action of TNF clearly reduces its inflammatory potential on various autoimmune disorders like Crohn s disease, rheumatoid arthritis (RA), and psoriasis. 

For many years, alterations in APOE and defects in the APOE gene have been associated with dysfunctions in lipid metabolism, cardiovascular disease, and atherosclerosis. During the past 25 years, an enormous amount of studies clearly documented the role of APOE-4 as a risk factor for AD, and the accumulation of the APOE-4 allele has been reported as a risk factor for other forms of dementia and CNS disorders (1,12,18-20,47.488). 

Cardiovascular and cerebrovascular disorders associated with lipid metabolism disturbance and atherosclerosis represent major risk factors for dementia (3,25,59). Atherosclerosis is the primary cause of heart disease and stroke in which genetic and environmental factors converge (553). More than 90% of patients older than 70-80 yr with dementia show signs of atherosclerosis in their arteries and a clear cerebrovascular component in their dementia process. It is very likely that pure AD is practically absent in octogenarians, in whom the prevalent diagnosis is vascular or mixed dementia (3,25,59), in which the APOE-4 allele also accumulates (18-20,554). 

All of these biological roles of the steroids figure prominently in human well-being. Defects in cholesterol metabolism are major causes of cardiovascular disease. It is no wonder that steroids are a central concern in medical biochemistry. In this chapter we discuss the metabolism of these complex lipids and the plasma lipoproteins in which they and other complex lipids are transported to various tissues. 

Certain bioflavonoids may play a preventive role against cardiovascular diseases. Some citrus and other bioflavonoids have been demonstrated to reduce serum cholesterol levels and to affect fatty acid metabolism (70,71,72). The strong antiadhesive action on red cells and platelets of highly methoxylated flavones such as nobiletin, which also demonstrates antithrombogenic activity (73), indicates an important role in blood rheology and tissue perfusion. The antiadhesive action may indicate a preventive role in atherosclerosis since there is evidence that reduced perfusion of the vascular wall may interact with serum lipids to promote atherogenesis (74). 

Depression and Metabolic Syndrome. Abnormal serum albumin levels and lipid profiles have both been observed in patients with major depression, as well as cardiovascular disease, diabetes mellitus, and end-stage renal disease. Depressive symptoms are very common in patients with these chronic illnesses. Recent clinical data have shown that cardiovascular disease, diabetes mellitus, end-stage renal disease, and obesity are all related to metabolic syndromes [68-74], and especially insulin resistance [75, 76]. However, the data examining major depression without physical illness and insulin resistance are still scarce. In the future, the biological relationship between depression and physical illness needs to be more fully explored. 

Rosmond and Bjorntorp also addressed the potential effect of HPA axis activity on established anthropometric, metabolic, and hemodynamic risk factors for cardiovascular disease, type 2 diabetes mellitus, and stroke [112], Strong and consistent correlations were found not only within but also between different clusters of risk factors, including lipid profiles [110]. The close association to HPA axis abnormality may explain the previously reported powerful risk indication of abdominal obesity for the diseases mentioned under environmental stress challenges [112]. 

Increased levels of ROS due to oxidative stress have been consistently found in cardiovascular diseases as atherosclerosis or hypertension [18]. There is certain evidence that the free radicals involved in Parkinson s disease are mainly due to the production of increased levels of free radicals during oxidative metabolism of dopamine [19]. Oxidative stress, manifested by protein oxidation and lipid peroxidation (LP), among other alterations, is a characteristic of Alzheimer s disease [20] and in the pathogenesis of diabetes related complications. Treatment with antioxidants seemed to be a promising therapeutic option for these diseases [21], The inflammatory nature of rheumatoid arthritis implies that a state of oxidative stress may also exist in this disease [22,23]. Also, free radicals have a certain role in Huntington s disease [24,25], age related degeneration [26], and some autoimmune disorders [27],... 

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