Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypothyroidism may result in accelerated atherosclerosis. Hyperhomocysteinaemia is an independent risk factor for premature atherosclerotic vascular disease. The aim of the present study was to assess plasma total homocysteine (tHcy), folate and cobalamin concentrations in hypothyroid patients before and after treatment. Thirty-one hypothyroid and thirty health young women were studied. The hypothyroid patients were investigated in the untreated state and again after restoration of euthyroidism. The levels of homocysteine, folate, cobalamin and thyroid stimulating hormone (TSH), free thyroxine (fT(4)), free triiodothyronine (fT(3)) and renal function were measured before and after treatment. In hypothyroidism tHcy was higher but not statistically significant than in control group. Serum level of folate was higher and serum cobalamin was lower in the hypothyroid state. Following L-thyroxine therapy tHcy significantly decreased as well as the concentration of cobalamin. Level of folate remained unchanged. Univariate analysis in hypothyroid group indicated that tHcy negative correlated with creatinine clearance, fT(3), fT(4), cobalamin and positive with TSH. In multivariate analysis tHcy correlated with creatinine clearance, cobalamin and fT(4). Thyroid status influences the plasma tHcy. Free triiodothyronine and next free thyroxine have the greatest negative influence. This would account for hyperhomocysteinemia in the hypothyroid state and premature atherogenesis.
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PMID:Homocysteine, folate and cobalamin levels in hypothyroid women before and after treatment. 1746 93

Controversy remains as to the risk of cardiovascular disease (CVD) associated with subclinical hypothyroidism (SCH), defined as an increased serum thyrotropin (TSH) concentration with normal free thyroxine and triiodothyronine levels. Substantial evidence indicates altered cholesterol and lipoprotein metabolism in SCH when serum TSH is above 10 mU/L. Observed abnormalities include elevated plasma levels of total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C); the altered TC/high-density lipoprotein-cholesterol (HDL-C) and LDL-C/HDL-C ratios suggest a potential accelerated risk for CVD. The influence of SCH on lipids is directly proportional to the degree of TSH elevation and becomes more significant with the progression from SCH to overt disease, thereby accelerating any propensity to atherosclerosis. Although many clinicians may tend to ignore SCH with TSH levels <10, it is apparent that an enhanced CV risk could apply to these individuals, perhaps compounded by insulin resistance and amplified by the copresence of other risk factors such as endothelial dysfunction and elevated C-reactive protein.
Thyroid 2007 Nov
PMID:Cardiovascular risk and subclinical hypothyroidism: focus on lipids and new emerging risk factors. What is the evidence? 1790 Feb 36

Chemokines are low-molecular-weight proteins that attract leukocytes and other cell types, via interaction with G protein-coupled receptors. Chemokines control leukocyte migration not only during inflammatory processes, but also throughout ontogeny and differentiation of lymphoid tissues. They have been involved in the pathogenesis of numerous diseases, such as human immunodeficiency virus infection, allergy, atherosclerosis, cancer, and autoimmunity. The number of studies focusing on chemokine biology is expanding exponentially. For example, searching PubMed for the terms "thyroid" and "chemokine" retrieved 1 article in 1980s, 18 articles in 1990s, and 81 articles from 2000 to July 2007. This review will focus on studies analyzing the role of chemokine in autoimmune thyroiditis (Graves' disease and Hashimoto's thyroiditis), performed in both patients and experimental animals. The goal is to emphasize how a better understanding of chemokine biology has advanced our knowledge of the pathogenesis of autoimmune thyroiditis.
Thyroid 2007 Oct
PMID:Chemokine orchestration of autoimmune thyroiditis. 1791 May 27

Thyroid hormones are essential to maintain normal function of many systems including the cardiovascular system. Their excess or deficiency may upset human body homeostasis. Hyperthyroidism leads to cardiovascular system's hyperdynamic status which is characterized by tachycardia, increased difference between systolic and diastolic arterial pressure, significant increase of the stroke volume and improvement of the left ventricular diastolic function. Long-lasting thyrotoxicosis in patient with heart disease may result in atrial fibrillation, deterioration of angina pectoris or congestive heart failure. Hypothyroidism leads to hemodynamic disturbances which are quite different than those observed in hyperthyroidism, but cardiac symptoms are scant in clinical practice. Hypothyroidism's clinical significance is limited to atherosclerosis progression and intensification of ischaemic heart disease symptoms. Both leads to symptomatic cardiovascular system failure or its deterioration. We should emphasize that cardiovascular system dysfunction associated with thyrometabolic disturbances subsides when euthyreosis is restored. It sounds promising that there are reports suggesting a potential advantage of thyroxin treatment in patients with acute or chronic cardiovascular system diseases. These hypotheses result from the observations that heart dysfunction in hypothyroidism is similar to that observed in heart failure.
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PMID:[Thyrometabolic disorders and heart failure]. 1794 Sep 89

Thyroid hormones have many effects on the heart and vascular system. Although cardiac output is reduced in hypothyroidism, heart failure is relatively rare because there is a lower demand for peripheral oxygen delivery. Hypothyroidism may also result in accelerated atherosclerosis and coronary artery disease. We report the case of a 55-year-old man with severe heart failure associated with severe longstanding untreated hypothyroidism. The patient was admitted for shortness of breath and chest pain. On presentation, signs and symptoms of severe hypothyroidism and heart failure were noticed. The electrocardiogram showed sinus bradycardia and ischemia. Thyroid stimulating hormone was extremely elevated and thyroid hormone levels were undetectable. A cardiac ultrasonography exam revealed abnormalities of the left ventricular dimensions and function consistent with dilated cardiomyopathy. Coronary angiography showed severe multivessel disease. Coronary by-pass was deemed necessary, but surgery was postponed because of severe heart failure. After an increasingly downhill clinical course, the patient died, eight month after his initial presentation, owing to severe heart failure. This patient represents an example of an overlooked diagnosis of severe hypothyroidism, rarely encountered nowadays, leading to dramatic consequences.
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PMID:Heart failure and dilated cardiomyopathy associated with severe longstanding untreated hypothyroidism. 1796 46

Overt hypothyroidism (OH) and subclinical hypothyroidism (SH) are frequently found in the elderly. OH is associated with several functional cardiovascular abnormalities and increased risk of atherosclerosis resulting from hypertension associated to atherogenic lipid profile. Other potential atherogenic factors involved in OH are increased circulating C-reactive protein and homocysteine, increased arterial stiffness, endothelial dysfunction, and altered coagulation parameters. Similar (although mild) cardiovascular abnormalities are present in SH. Since all these abnormalities regress with levothyroxine (L-T4) administration, the cardiovascular benefits of replacement therapy in OH are not questionable, independently from the patient's age or the presence of coexisting cardiovascular disease. On the other hand, in spite of a very large number of studies, no consensus has been reached so far about the actual cardiovascular and/or general health impact of SH, and different recommendations have been recently made about screening and treatment of this condition. Although divergent results have been obtained in several epidemiological studies, recent meta-analyses provide evidence for a slight but significant increase of coronary heart disease (CHD) risk in SH. However, no agreement has been reached in favor or against active screening and/or treatment of mild thyroid failure. Moreover, L-T4 therapy is discouraged in aged subjects, because the increased oxygen consumption consequent to thyroid hormone administration could be dangerous, especially in the presence of coexisting CHD. In keeping with this concept are recent data showing reduced mortality risk in untreated mild hypothyroid subjects aged >85 years, suggesting that some degree of decreased thyroid activity at the tissue level might have favorable effects in the oldest-old. However, the effects of subtle thyroid dysfunction may be different in different age ranges. Since the main studies supporting a role for SH as a risk factor for atherosclerosis, cardiovascular disease, and all-cause mortality have been carried out in populations aged > or =55-60 years, mild thyroid failure could concur to increased cardiovascular risk in middle-aged and "young elderly" subjects, while being devoid of detrimental effects and possibly protective in the oldest-old. Further studies are needed to confirm this hypothesis.
Thyroid 2007 Nov
PMID:Cardiovascular risk in elderly hypothyroid patients. 1804 29

Atherosclerotic cardiovascular disease is a major problem despite the availability of drugs that influence major risk factors. New treatments are needed, and there is growing interest in therapies that may have multiple actions. Thyroid hormone modulates several cardiovascular risk factors and delays atherosclerosis progression in humans. However, use of thyroid hormone is limited by side effects, especially in the heart. To overcome this limitation, pharmacologically selective thyromimetics that mimic metabolic effects of thyroid hormone and bypass side effects are under development. In animal models, such thyromimetics have been shown to stimulate cholesterol elimination through LDL and HDL pathways and decrease body weight without eliciting side effects. We report here studies on a selective thyromimetic [KB2115; (3-[[3,5-dibromo-4-[4-hydroxy-3-(1-methylethyl)-phenoxy]-phenyl]-amino]-3-oxopropanoic acid)] in humans. In moderately overweight and hypercholesterolemic subjects KB2115 was found to be safe and well tolerated and elicited up to a 40% lowering of total and LDL cholesterol after 14 days of treatment. Bile acid synthesis was stimulated without evidence of increased cholesterol production, indicating that KB2115 induced net cholesterol excretion. KB2115 did not provoke detectable effects on the heart, suggesting that the pharmacological selectivity observed in animal models translates to humans. Thus, selective thyromimetics deserve further study as agents to treat dyslipidemia and other risk factors for atherosclerosis.
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PMID:The thyroid hormone mimetic compound KB2115 lowers plasma LDL cholesterol and stimulates bile acid synthesis without cardiac effects in humans. 1818 79

Controlling iron/oxygen chemistry in biology depends on multiple genes, regulatory messenger RNA structures, signaling pathways and protein catalysts. Ferritin synthesis is regulated by cytokines (tumor necrosis factor-alpha and interleukin-1alpha) at various levels (transcriptional, post-transcriptional, translational) during development, cellular differentiation, proliferation and inflammation. The cellular response by cytokines to infection stimulates the expression of ferritin genes. The immunological actions of ferritin include binding to T lymphocytes, suppression of the delayed-type hypersensitivity, suppression of antibody production by B lymphocytes, and decreased phagocytosis of granulocytes. Thyroid hormone, insulin and insulin growth factor-1 are involved in the regulation of ferritin at the mRNA level. Ferritin and iron homeostasis are implicated in the pathogenesis of many disorders, including diseases involved in iron acquisition, transport and storage (primary hemochromatosis) as well as in atherosclerosis, Parkinson's disease, Alzheimer disease, and restless leg syndrome. Mutations in the ferritin gene cause the hereditary hyperferritinemia-cataract syndrome and neuroferritinopathy. Hyperferritinemia is associated with inflammation, infections and malignancies, and in systemic lupus erythematosus correlates with disease activity. Some evidence points to the importance of hyperferritinemia in dermatomyositis and multiple sclerosis, but further mechanistic investigations are warranted.
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PMID:Hyperferritinemia in autoimmunity. 1830 May 83

To investigate the relationship between thyroid function and carotid intima-media thickness (CIMT) in a relatively large general population with euthyroid status we initially enrolled 1772 Japanese adults (421 men and 1351 women) who participated in a medical screening program for the general population over 40 years old. To evaluate only euthyroid subjects without vascular diseases and/or its major risk factors, 1129 were excluded and 643 participants (175 men and 468 women) were included for further analysis. Simple and multivariate linear regression analyses were performed to evaluate free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels and other existing parameters, including carotid intima-media thickness. By multivariate linear regression analysis adjusted for age and sex, free thyroxine was significantly correlated with triglycerides (beta=0.07, p=0.015), carotid intima-media thickness (beta=-0.091, p=0.049), and thyroid-stimulating hormone (beta=-0.091, p=0.003). Thyroid-stimulating hormone was significantly correlated with high-density lipoprotein cholesterol (HDL-C) (beta=-0.001, p=0.015), HbA(1c) (beta=0.038, p=0.045), carotid intima-media thickness (beta=0.27, p=0.001), and free thyroxine (beta=-0.15, p=0.003). When adjusted for confounding factors, free thyroxine was significantly correlated only with carotid intima-media thickness (beta=-0.13, p=0.043) and thyroid-stimulating hormone was significantly correlated with HDL-C (beta=-0.001, p<0.001), HbA(1c) (beta=0.04, p=0.021), and carotid intima-media thickness (beta=0.29, p=0.001). We have demonstrated that carotid intima-media thickness is independently associated with thyroid function within the normal reference range, which suggests an increased cardiovascular risk in subjects with low normal thyroid function.
Atherosclerosis 2009 Jun
PMID:Thyroid function is associated with carotid intima-media thickness in euthyroid subjects. 1897 82

Thyroid hormones influence heart rate, serum lipids, metabolic rate, body weight and multiple aspects of lipid, carbohydrate, protein and mineral metabolism. Although increased thyroid hormone levels can improve serum lipid profiles and reduce fat, these positive effects are counterbalanced by harmful effects on the heart, muscle and bone. Thus, attempts to use thyroid hormones for cholesterol-lowering and weight loss purposes have so far been limited. However, over the past decade, thyroid hormone analogues that are capable of uncoupling beneficial effects from deleterious effects have been developed. Such drugs could serve as powerful new tools to address two of the largest medical problems in developed countries--atherosclerosis and obesity.
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PMID:Thyroid hormone mimetics: potential applications in atherosclerosis, obesity and type 2 diabetes. 1933 72


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