Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apolipoprotein (apo) E is associated with several classes of lipoproteins and serves as a ligand for the receptor mediated uptake of cholesterol-rich particles by hepatocytes and peripheral tissues. Variant forms of apo E is also associated with dyslipidemia and late-onset of Alzheimer's Disease (AD). We report here expression of apoE in various mouse tissues, and regulation of apoE in liver, kidney, brain and testes by supraphysiological doses of estrogen. ApoE mRNA was quantified by RNase protection assay and translatable apoE mRNA by in vitro translation. As an internal control the levels of beta-actin mRNA were also quantified. Highest levels of apoE were expressed in liver (220-280 pg/mu g RNA) with negligible levels in small intestine. Brain expressed highest levels of total (35-40 pg/mu g RNA) and translatable apoE mRNA next only to liver. Other tissues that expressed relatively higher levels of apoE were adrenals, testes and ovary. ApoE was also found to be expressed in heart, lung, kidney and spleen. Regulation of apoE gene expression by estrogen (3 mu g 17beta-estradiol/ g body weight/ day for 5 consecutive days) was studied in liver, kidney, brain and testes of 4 mouse strains. Hepatic apoE mRNA did not change significantly in any of the mouse strains following estradiol administration. Of note was significant increases in the levels of brain apoE mRNA in the strain C3H. These studies demonstrate that estrogen regulates apoE gene expression in a tissue-specific manner in mice, and increases in apoE mRNA in the brain by estrogen may have implications in late-onset of Alzheimer's Disease.
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PMID:Apolipoprotein E gene expression in various tissues of mouse and regulation by estrogen. 893 23

Apolipoprotein E (apo E) deficiency (or its abnormalities in humans) is associated with a series of pathological conditions including dyslipidemia, atherosclerosis, Alzheimer's disease, and shorter life span. The purpose of this study was to characterize these conditions in apo E-deficient C57BL/6J mice and relate them to human disorders. Deletion of apo E gene in mice is associated with changes in lipoprotein metabolism [plasma total cholesterol (TC) (>+400%), HDL cholesterol (-80%), HDL/TC, and HDL/LDL ratios (-93% and -96%, respectively), esterification rate in apo B-depleted plasma (+100%), plasma triglyceride (+200%), hepatic HMG-CoA reductase activity (-50%), hepatic cholesterol content (+30%)], decreased plasma homocyst(e)ine and glucose levels, and severe atherosclerosis and cutaneous xanthomatosis. Hepatic and lipoprotein lipase activities, hepatic LDL receptor function, and organ antioxidant capacity remain unchanged. Several histological/immunohistological stainings failed to detect potential markers for neurodegenerative disease in the brain of 37-wk-old male apo E-KO mice. Apo E-KO mice may have normal growth and development, but advanced atherosclerosis and xanthomatosis may indirectly reduce their life span. Apo E plays a crucial role in regulation of lipid metabolism and atherogenesis without affecting lipase activities, endogenous antioxidant capacity, or appearance of neurodegenerative markers in 37-wk-old male mice.
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PMID:Pathophysiology of apolipoprotein E deficiency in mice: relevance to apo E-related disorders in humans. 1172 38

The review covers principles of treatment with statins, their pharmacokinetics, characterizes six most usable in clinical practice statins and one novel drug--rozuvastatin from a "superstatins" group. Statins proved effective in primary and secondary prophylaxis of coronary atherosclerosis, secondary prevention of ischemic stroke and diseases of peripheral arteries with intermittent claudication, prevention of Alzheimer's disease. Statins are indicated in dyslipidemia in diabetes mellitus type 2, nephrotic syndrome and renal insufficiency. Further studies are needed on statins' effects on hypercholesterolemia, their antiinflammatory and immunomodulating properties, the ability to enhance revascularization of ischemic tissue and stimulate proliferation of osteoblasts in osteoporosis.
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PMID:[Statins in clinical practice]. 1208 96

Vascular dementia (VaD) and Alzheimer's disease (AD) are the most common causes of dementia in the elderly. The aim of this study was to investigate carotid atherosclerosis, serum lipid profiles, and atherogenic hormone levels in nondiabetic Japanese men with VaD or AD. Carotid artery intima-media thickness (IMT) and plaque, serum lipid and lipoprotein profiles, including low-density lipoprotein (LDL) particle size, as well as insulin-like growth factor-I (IGF-I, somatomedin C) and testosterone levels, were determined in 34 patients with AD, 37 patients with VaD, and 63 healthy male controls. Age, body mass index, systolic and diastolic blood pressure, and fasting plasma glucose, hemoglobin A(1c) (HbA(1c)), triglyceride, high-density lipoprotein (HDL)-cholesterol, and apolipoproteins (apo) A-I, B, and E levels did not differ significantly among the 3 groups. However, the mean value of carotid IMT, the frequency of atherosclerotic plaque deposition, the serum levels of LDL-cholesterol, lipoprotein(a), and lipid peroxides, and the incidence of small dense LDL (particle diameter </= 25.5 nm) were increased significantly in VaD patients compared with AD patients or controls. VaD patients had a close reverse correlation between carotid IMT and LDL particle diameter, which were statistically proven independent risk factors for VaD. In contrast, AD patients had significantly lower serum levels of IGF-I and testosterone than either VaD patients or controls. Our results indicate that VaD is associated with atherogenic dyslipidemia, in particular, small dense LDL and carotid atherosclerosis, whereas AD is associated with hyposomatomedinemia and hypogonadism rather than atherosclerosis.
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PMID:Small dense low-density lipoprotein and carotid atherosclerosis in relation to vascular dementia. 1504 95

The insulin resistance syndrome (syndrome X, metabolic syndrome) has become the major health problem of our times. Associated obesity, dyslipidemia, atherosclerosis, hypertension, and type 2 diabetes conspire to shorten life spans, while hyperandrogenism with polycystic ovarian syndrome affect the quality of life and fertility of increasing numbers of women. Whereas a growing number of single genetic diseases affecting satiety or energy metabolism have been found to produce the clinical phenotype, strong familial occurrences, especially in racially prone groups such as those from the Indian subcontinent, or individuals of African, Hispanic, and American Indian descents, together with emerging genetic findings, are revealing the polygenetic nature of the syndrome. However, the strong lifestyle factors of excessive carbohydrate and fat consumption and lack of exercise are important keys to the phenotypic expression of the syndrome. The natural history includes small for gestational age birth weight, excessive weight gains during childhood, premature pubarche, an allergic diathesis, acanthosis nigricans, striae compounded by gynecomastia, hypertriglyceridemia, hepatic steatosis, premature atherosclerosis, hypertension, polycystic ovarian syndrome, and focal glomerulonephritis appearing increasingly through adolescence into adulthood. Type 2 diabetes, which develops because of an inherent and/or an acquired failure of an insulin compensatory response, is increasingly seen from early puberty onward, as is atheromatous disease leading to coronary heart disease and stroke. A predisposition to certain cancers and Alzheimer's disease is also now recognized. The looming tragedy from growing numbers of individuals affected by obesity/insulin resistance syndrome requires urgent public health approaches directed at their early identification and intervention during childhood. Such measures include educating the public on the topic, limiting the consumption of sucrose-containing drinks and foods with high carbohydrate and fat contents, and promoting exercise programs in our nation's homes and schools.
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PMID:Insulin resistance syndrome in children. 1518 Oct 20

Although hyperlipidemia is known to contribute to vascular disease and it may play a role in dementia, specific studies for elderly are limited. The aim of this study is to examine the relationship between dyslipidemia and dementia. In this study, 1251 patients admitted to the Hacettepe University Division of Geriatric Medicine were enrolled. On the basis of the mini mental state examination (MMSE), the clock drawing test (CDT) scores, the APA DSM-IV and the NINCDS-ADRDA criteria and the Hachinski ischemic score (HIS), the subjects were divided into four groups: Alzheimer's disease (AD), vascular dementia (VD), mild cognitive impairment (MCI) and normal cognitive status (NCS). The lipoprotein levels were measured, and we analyzed the data using chi2 and the one-way analysis of variance methods. Among the subjects, 14.8% had low high-density lipoproteins (HDL), 58.5% had high triglyceride (TG), 73.6% had high low-density lipoproteins (LDL), and 21.6% had high lipoprotein-a (Lp(a)) of our study population. There was no difference between the dementia subgroups and the NCS group in the lipoprotein levels. The only significant relationship was between high TG levels and the AD, as well as the MCI groups. Low HDL and high LDL are important problems in elderly. Although serum lipid levels, especially of Lp(a), has recently been thought to be related with dementia, our study suggests the absence of such a relationship. The national data regarding the elderly population should be evaluated on the basis of genetic and environmental factors in each country. The present study showing no significant relationship between Lp(a) and the cognitive status adds new information to the available literature.
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PMID:Are serum lipid and lipoprotein levels related to dementia? 1591 Oct 36

Vascular cognitive impairment encompasses a spectrum of clinically defined syndromes ranging from vascular cognitive impairment-no dementia, to vascular dementia. The underlying cerebrovascular pathology includes both overt infarction as well as rarefaction of gray and white matter. Alzheimer's pathology may coexist with vascular pathology. Diagnosis rests on identifying acquired cognitive impairment in the setting of documented cerebrovascular disease, based on clinical presentation and neuroimaging; MRI is more sensitive than CT. The course can be stepwise or gradually progressive. The clinical picture is typically dominated by deficits in executive function rather than the short-term memory deficit typical of Alzheimer's disease. No specific therapies exist, but treatment with anticholinesterase agents and N-methyl-d-aspartate antagonists may result in clinical improvement. Prevention remains paramount, with early recognition of populations at risk and early and aggressive management of risk factors, including hypertension, dyslipidemia, diabetes, and tobacco use as well as antithrombotic therapy, in appropriate populations.
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PMID:Vascular cognitive impairment. 1663 44

Alzheimer's disease (AD) is a heterogeneous neurodegenerative disorder characterized pathologically by amyloid-beta plaques, neurofibrillary tangles and neuronal loss. Its fundamental cause(s) and the pathological cascades leading to clinical symptoms remain unknown. Lipids and lipid peroxidation products have important roles in the homeostasis of the central nervous system. As well, lipid transport genes and vascular changes associated with peripheral dyslipidemia have been associated with an increased risk of AD. The present review discusses ways in which lipids may be involved in the pathogenesis of AD-associated neurodegeneration through their roles as neuronal structural components, cell modulators, or second messengers. Given the many possibilities through which lipids may be directly involved in or contribute to the pathogenesis of AD, the use of lipids as biomarkers for disease progression is discussed, as are other avenues for future research.
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PMID:Lipids and the pathogenesis of Alzheimer's disease: is there a link? 1677 71

High fat diets and sedentary lifestyles are becoming major concerns for Western countries. They have led to a growing incidence of obesity, dyslipidemia, high blood pressure, and a condition known as the insulin-resistance syndrome or metabolic syndrome. These health conditions are well known to develop along with, or be precursors to atherosclerosis, cardiovascular disease, and diabetes. Recent studies have found that most of these disorders can also be linked to an increased risk of Alzheimer's disease (AD). To complicate matters, possession of one or more apolipoprotein E epsilon4 (APOE epsilon4) alleles further increases the risk or severity of many of these conditions, including AD. ApoE has roles in cholesterol metabolism and Abeta clearance, both of which are thought to be significant in AD pathogenesis. The apparent inadequacies of ApoE epsilon4 in these roles may explain the increased risk of AD in subjects carrying one or more APOE epsilon4 alleles. This review describes some of the physiological and biochemical changes that the above conditions cause, and how they are related to the risk of AD. A diversity of topics is covered, including cholesterol metabolism, glucose regulation, diabetes, insulin, ApoE function, amyloid precursor protein metabolism, and in particular their relevance to AD. It can be seen that abnormal lipid, cholesterol and glucose metabolism are consistently indicated as central in the pathophysiology, and possibly the pathogenesis of AD. As diagnosis of mild cognitive impairment and early AD are becoming more reliable, and as evidence is accumulating that health conditions such as diabetes, obesity, and coronary artery disease are risk factors for AD, appropriate changes to diets and lifestyles will likely reduce AD risk, and also improve the prognosis for people already suffering from such conditions.
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PMID:Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer's disease and cardiovascular disease. 1678 33

Evidence will be presented to support the usefulness of the altered homeostatic theory in understanding basic pathogenetic mechanisms of ischemic heart disease (IHD), hypertension, and diabetes, and in improving prevention of these disorders. The theory argues that: IHD, hypertension, and diabetes share the same basic pathogenesis; risk factors favor a sympathetic homeostatic shift; preventative factors favor a parasympathetic homeostatic shift; risk and preventative factors oppose each other through a dynamic risk/prevention balance; and prevention should be based on improving the risk/prevention balance. Prevention based on improving the risk/prevention balance should be more effective, as this method is regarded as reflecting more accurately basic pathogenetic mechanisms. As example, the theory argues that the risk of supposedly nonmodifiable risk factors as age and the risk of relatively nonmodifiable atherosclerosis can be reduced significantly. The possible validity of the altered homeostatic theory was tested by a study based on multiple associations. Findings support a common pathogenesis for IHD, hypertension, and diabetes based on a sympathetic homeostatic shift, and the usefulness of prevention based on improving the risk/prevention balance by using standard pharmaceutical and lifestyle preventative measures. The same set of multiple and diverse risk factors favored IHD, hypertension, and diabetes, and the same set of multiple and diverse pharmaceutical and lifestyle preventative measures prevented these disorders. Also, the same set of preventative agents generally improved cognitive function and bone density, and reduced the incidence of Alzheimer's disease, atrial fibrillation, and cancer. Unexpectedly, evidence was developed that four major attributes of sympathetic activation represent four major risk factors; attributes of sympathetic activation are a tendency toward thrombosis and vasoconstriction, lipidemia, inflammation, and hyperglycemia, and corresponding risk factors are endothelial dysfunction (which expresses thrombosis/vasoconstriction and epitomizes this tendency), dyslipidemia, inflammation, and insulin resistance. These findings, plus other information, provide evidence that dyslipidemia acts mainly as a marker of risk of IHD, rather than being the basic mechanism of this disorder. However, prevention generally is based solely on improvement of dyslipidemia; basing prevention on dyslipidemia relatively underemphasizes the importance of other significant risk factors and, by certifying its validity, discourages alternate pathogenetic approaches. Also, development of myocardial infarction is approached differently. It seems generally accepted that dyslipidemia results rather automatically in infarction through the sequence of atherosclerosis, atherosclerotic complications, and thrombosis. In contrast, distinction is made between development of atherosclerosis and acute induction of infarction--where atherosclerosis is only one of multiple risk factors.
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PMID:The altered homeostatic theory: A hypothesis proposed to be useful in understanding and preventing ischemic heart disease, hypertension, and diabetes--including reducing the risk of age and atherosclerosis. 1870 71


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