Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An accurate study on the alterations of lipid metabolism was made on a sample of 30 patients affected by senile macular degeneration and 13 patients affected by senile macular degeneration complicated by retinopathy due to hyperlipidemia. The authors came to the conclusion that hyperlipidemia can complicate simple macular degeneration, even if a close correlation between the two phenomena can be excluded.
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PMID:Senile macular degeneration and alteration of the metabolism of the lipids. 74 Mar 55

Ocular vascular diseases such as diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration, whose population increases along with aging, have become leading causes of severe visual disturbance. Macular edema and serous retinal detachment are associated with abnormal vascular leakage and tractional retinal detachment, and neovascular glaucoma is caused by retinal neovascularization. Such ocular vascular diseases are caused by vascular cell aging and vascular damage associated with lifestyle-related diseases including diabetes mellitus, hypertension, hyperlipidemia, and obesity. In the present study, we investigated molecular mechanisms in such vascular deficiencies using vascular cell biology methodology, and we propose novel strategies for the treatment of such vascular diseases. Along with aging, oxidative stress and physical stress, such as mechanical stretch, continuously and directly insult vascular cells. Such stress induces apoptosis by intracellular signaling through stress kinases in cultured retinal vascular cells. Inhibition of such stress kinases could be an effective treatment to protect the vascular cells against age-related damage. In a retinal vascular developmental model, pericyte loss causes pathology mimicking macular edema and proliferative diabetic retinopathy. Angiopoietin 1 (Ang 1) secreted by pericytes suppresses oxidative stress-induced intracellular signaling through stress kinases linked to cell apoptosis and normalizes such retinal pathology. This suggests that the paracrine action of Ang 1 in the pericytes is necessary to sustain normal retinal vasculature, and that Ang 1-triggered intracellular signaling is useful for the treatment of vascular cell pathology associated with pericyte loss. In diabetic retinopathy and retinal vein occlusion, retinal vessels regress along with retinal vascular cell apoptosis, and the retina becomes ischemic followed by pathological retinal neovascularization. VEGF has been recognized as a predominant factor to induce the ischemic retinal neovascularization. We found that retinal vascular cells have a characteristic pattern in VEGF receptor expression, which causes vascular pathology more frequently in the retina than in other organs. Neuropilin 1 (NRP 1), which enhances VEGF receptor function, is abundantly expressed in the retinal endothelial cells and is upregulated by VEGF itself and by hypoxia to regulate a positive feedback mechanism in retinal neovascularization. This receptor could be a unique target for retina-specific therapy. Lifestyle-related diseases increase along with aging and have further increased due to changes in Japanese lifestyle imitating that of Western countries. We found that the renin-angiotensin system which regulates hypertension and cardiovascular diseases, and adipocytokines which are abnormally secreted in obesity, act as proangiogenic factors. Regulation of such lifestyle-related disease factors is important for the treatment of retinal vascular diseases. Finally, we found that erythropoietin is an ischemia-induced angiogenic factor that acts independently and as potently as VEGF in proliferative diabetic retinopathy (PDR). Our study utilizing human vitreous samples demonstrates that the VEGF level is particularly high and strongly associated with angiogenic activity in PDR patients. The potential of VEGF inhibitors has recently been recognized in clinical applications. The manipulation of each angiogenic factor and adipocytokine that we report here could become potential therapy in the near future.
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PMID:[Aging and retinal vascular diseases]. 1740 63

Family physicians have an essential role in assessing, identifying, treating, and preventing or delaying vision loss in the aging population. Approximately one in 28 U.S. adults older than 40 years is visually impaired. Vision loss is associated with depression, social isolation, falls, and medication errors, and it can cause disturbing hallucinations. Adults older than 65 years should be screened for vision problems every one to two years, with attention to specific disorders, such as diabetic retinopathy, refractive error, cataracts, glaucoma, and age-related macular degeneration. Vision-related adverse effects of commonly used medications, such as amiodarone or phosphodiesterase inhibitors, should be considered when evaluating vision problems. Prompt recognition and management of sudden vision loss can be vision saving, as can treatment of diabetic retinopathy, refractive error, cataracts, glaucoma, and age-related macular degeneration. Aggressive medical management of diabetes, hypertension, and hyperlipidemia; encouraging smoking cessation; reducing ultraviolet light exposure; and appropriate response to medication adverse effects can preserve and protect vision in many older persons. Antioxidant and mineral supplements do not prevent age-related macular degeneration, but may play a role in slowing progression in those with advanced disease.
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PMID:Vision loss in older persons. 1951 94

Since the introduction of HMG-CoA reductase inhibitors (statins) for lowering lipids, a large amount of data has been published demonstrating their potential benefits in conditions as varied as cancer, osteoporosis, and Alzheimer's dementia. We reviewed the published literature on MEDLINE from articles between 1950 and 2008 on the non-atheroprotective effects of statins and noted consistent benefits of statin use in improving outcomes of ventricular arrhythmias, sudden cardiac death, cardiac transplant rejection, chronic obstructive pulmonary disease, and sepsis. However, for these conditions, the level of evidence was inadequate to recommend statin use. The evidence for improving outcomes in atrial fibrillation, mortality in heart failure, contrast-induced nephropathy, cataract, age-related macular degeneration, sub-arachnoid hemorrhage, osteoporosis, dementia, and cancer incidence was conflicting and inconclusive. Furthermore, we found that most of the literature consists of small observational studies and their conclusions are often not corroborated by results from larger or randomized studies. Pending large, well designed, randomized trials, we conclude that there is no definite evidence for the use of statins in any condition besides hyperlipidemia and atherosclerosis.
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PMID:Non-atheroprotective effects of statins: a systematic review. 1992 34

The glycemic index (GI) indicates how fast blood glucose is raised after consuming a carbohydrate-containing food. Human metabolic studies indicate that GI is related to patho-physiological responses after meals. Compared with a low-GI meal, a high-GI meal is characterized with hyperglycemia during the early postprandial stage (0-2h) and a compensatory hyperlipidemia associated with counter-regulatory hormone responses during late postprandial stage (4-6h). Over the past three decades, several human health disorders have been related to GI. The strongest relationship suggests that consuming low-GI foods prevents diabetic complications. Diabetic retinopathy (DR) is a complication of diabetes. In this aspect, GI appears to be useful as a practical guideline to help diabetic people choose foods. Abundant epidemiological evidence also indicates positive associations between GI and risk for type 2 diabetes, cardiovascular disease, and more recently, age-related macular degeneration (AMD) in people without diabetes. Although data from randomized controlled intervention trials are scanty, these observations are strongly supported by evolving molecular mechanisms which explain the pathogenesis of hyperglycemia. This wide range of evidence implies that dietary hyperglycemia is etiologically related to human aging and diseases, including DR and AMD. In this context, these diseases can be considered as metabolic retinal diseases. Molecular theories that explain hyperglycemic pathogenesis involve a mitochondria-associated pathway and four glycolysis-associated pathways, including advanced glycation end products formation, protein kinase C activation, polyol pathway, and hexosamine pathway. While the four glycolysis-associated pathways appear to be universal for both normoxic and hypoxic conditions, the mitochondria-associated mechanism appears to be most relevant to the hyperglycemic, normoxic pathogenesis. For diseases that affect tissues with highly active metabolism and that frequently face challenge from low oxygen tension, such as retina in which metabolism is determined by both glucose and oxygen homeostases, these theories appear to be insufficient. Several lines of evidence indicate that the retina is particularly vulnerable when hypoxia coincides with hyperglycemia. We propose a novel hyperglycemic, hypoxia-inducible factor (HIF) pathway, to complement the current theories regarding hyperglycemic pathogenesis. HIF is a transcription complex that responds to decrease oxygen in the cellular environment. In addition to playing a significant role in the regulation of glucose metabolism, under hyperglycemia HIF has been shown to increase the expression of HIF-inducible genes, such as vascular endothelial growth factor (VEGF) leading to angiogenesis. To this extent, we suggest that HIF can also be described as a hyperglycemia-inducible factor. In summary, while management of dietary GI appears to be an effective intervention for the prevention of metabolic diseases, specifically AMD and DR, more interventional data is needed to evaluate the efficacy of GI management. There is an urgent need to develop reliable biomarkers of exposure, surrogate endpoints, as well as susceptibility for GI. These insights would also be helpful in deciphering the detailed hyperglycemia-related biochemical mechanisms for the development of new therapeutic agents.
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PMID:Dietary hyperglycemia, glycemic index and metabolic retinal diseases. 2086 67

We evaluated the prevalence and risk factors for early age-related macular degeneration (AMD) in Koreans 50 yr of age or older who were examined at a single health promotion center. We retrospectively reviewed the records of 10,449 subjects who visited the center over a 6-month period. Fundus photography was performed on all subjects, and systematic risk factor analysis was conducted using a structured questionnaire. All patients (n = 322) were initially diagnosed with drusen or early AMD using fundoscopy; the control group (n = 10,127) were those yielding normal fundoscopy findings. The age- and gender-adjusted prevalence of early AMD was 3.08%. Advanced age, male gender, smoking status, hyperlipidemia, working outdoors, and residence in rural areas were all significantly associated with an increased risk for development of early AMD. Higher-level ingestion of fruit or herbal medication and an increased amount of exercise were associated with a lower risk of early AMD development. In our Korean cohort, consisting principally of relatively healthy, middle-class urban adults, the prevalence of early AMD was 3.08% that is similar to that reported in earlier epidemiological studies. Several modifiable risk factors such as smoking and hyperlipidemia are associated with the prevalence of early AMD in our cohort.
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PMID:Prevalence and risk factors of early-stage age-related macular degeneration in patients examined at a health promotion center in Korea. 2256 20

The aim of this study was to determine the relationship between the risk factors (age, obesity, hypertension, hyperlipidemia, smoking, consumption of alchohol and drugs, positive family history, and exposure to sunlight), coping with stress, psychological well-being and age-related macular degeneration (ARMD). Forty patients with ARMD (case group) and 63 presbyopes (control group) participated in the study. Patient data were collected through general information questionnaire including patient habits, the COPE questionnaire that showed the way the patients handling stress, and the GHQ that analyzed the psychological aspects of their quality of life. These questionnaires were administered to the patients during ophthalmologic examination. The study involved 46 (44.66%) men and 57 (55.33%) women. Statistical analysis showed that the major risks for the development of ARMD were elevated cholesterol, triglycerides and LDL cholesterol in plasma. A significantly higher number ofARMD patients had a positive family history when compared with presbyopes. This study showed presbyopes to cope with emotional problems significantly better and to have a lower level of social dysfunction when compared with ARMD patients. However, it is necessary to conduct further studies in a large number of patients to determine more accurately the pathophysiological mechanisms of metabolic factors as well as the impact of the disease on the quality of life in patients with ARMD.
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PMID:Metabolic risk factors, coping with stress, and psychological well-being in patients with age-related macular degeneration. 2497 69

Metabolic syndrome (MetS) is currently diagnosed by the co-presence of at least three of the five following abnormalities: abdominal obesity, dysglycaemia, elevated serum triglycerides, low high-density cholesterol (HDL) and finally elevated blood pressure. Metabolic syndrome increases the risk of developing cardiovascular disease and diabetes. This review is on the associations between MetS and vascular endothelial growth factor (VEGF). VEGF induces migration and proliferation of endothelial cells (ECs), increases vascular permeability and has a role in tumor growth, adipose tissue expansion, age-related macular degeneration and diabetic retinopathy. Circulating levels of VEGFs are elevated in obese individuals and it has also been suggested that VEGF is secreted from adipose tissues, especially from intra-abdominal adipose tissue. There is abundant evidence to support that poor glycemic control in diabetic patients is associated with increased plasma VEGF, which in turn may cause hypertension and several vascular complications in diabetic patients. Circulating VEGF levels are increased in children and young adults with type 1 diabetes mellitus and middle-aged diabetic patients with proliferative retinopathy. It has been revealed that plasma VEGF increases in patients with hyperlipidemia and may trigger the development of atherosclerosis. It can be concluded that there is a positive association between VEGF and components of MetS. Because of the importance of this relationship, more investigations are needed in this field.
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PMID:VEGF, the underlying factor for metabolic syndrome; fact or fiction? 2804 Apr 66

Phagocytosis of daily shed photoreceptor outer segments is an important function of the retinal pigment epithelium (RPE) and it is essential for retinal homeostasis. RPE dysfunction, especially impairment of its phagocytic ability, plays an essential role in the pathogenesis of age-related macular degeneration (AMD). Statins, or HMG CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, are drugs with multiple properties that have been extensively used to treat hyperlipidemia. However, their effect on RPE cells has not been fully elucidated. Here we report that high dose atorvastatin increased the phagocytic function of ARPE-19 cells, as well as rescue the cells from the phagocytic dysfunction induced by cholesterol crystals and oxidized low-density lipoproteins (ox-LDL), potentially by increasing the cellular membrane fluidity. Similar effects were observed when evaluating two other hydrophobic statins, lovastatin and simvastatin. Furthermore, atorvastatin was able to block the induction of interleukins IL-6 and IL-8 triggered by pathologic stimuli relevant to AMD, such as cholesterol crystals and ox-LDL. Our study shows that statins, a well-tolerated class of drugs with rare serious adverse effects, help preserve the phagocytic function of the RPE while also exhibiting anti-inflammatory properties. Both characteristics make statins a potential effective medication for the prevention and treatment of AMD.
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PMID:Atorvastatin Promotes Phagocytosis and Attenuates Pro-Inflammatory Response in Human Retinal Pigment Epithelial Cells. 2853 92

This study evaluated the effect of gout on the risk of dry eye disease (DED) by using the National Health Insurance Research Database (NHIRD). Data for 30,192 gout patients (21,081 men and 9111 women) and 30,192 non-gout patients (21,005 men and 9187 women) were analyzed. Approximately 1 million patients were randomly sampled from the NHIRD registry. After applying exclusion criteria, patients diagnosed with gout were enrolled in the study group. Thereafter, each individual in the study group underwent the matching process via the propensity score with another non-gout individual, which constituted the control group. The main outcome was defined as the development of DED in accordance with the corresponding International Classification of Diseases, Ninth Revision. In addition to DED, other risk factors including age, sex, and urbanization, and several co-morbidities were included in the multivariate model. The incidence of DED with the adjusted hazard ratio (aHR) and cumulative probability were evaluated in the gout and non-gout patients. A total of 2913 DED events were observed in the study group, whereas 2631 DED events were observed in the control group. A higher incidence rate ratio was found in the study group after adjustment (aHR: 1.065). Moreover, the cumulative probability indicated a significantly increased risk of DED in the study group (p = 0.001). The other potential risk factors of DED according to the multivariate analysis include older age, female gender, higher degree of urbanization, keratopathy, age-related macular degeneration, glaucoma, cataract, ischemic heart disease, hyperlipidemia, peripheral vascular disease, chronic pulmonary disease, rheumatic disease, peptic ulcer disease, liver disease, and malignancy. In conclusion, gout increased the risk of DED after adjustment, and the risk is positively correlated to a longer disease period.
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PMID:Gout as a Risk Factor for Dry Eye Disease: A Population-Based Cohort Study. 3063 89


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