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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adult growth hormone (GH) deficiency is associated with a lipid profile known to be related to atherosclerosis. GH replacement therapy improves the lipid profile with the exception of lipoprotein (a) concentrations, which tend to increase after GH therapy. Plasma lipid concentrations depend on its plasma carriers, the lipoproteins. Possible mechanisms involved in the dyslipidaemia of GH-deficient patients and the effects of GH replacement therapy are discussed with a special focus on hepatic lipoprotein metabolism.
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PMID:Dyslipidaemia in Adult Growth Hormone (GH) Deficiency and the Effect of GH Replacement Therapy: A Review. 1840 66

Liver X receptors (LXRs), activated by oxysterols, play an important role in the regulation of lipid and glucose metabolism, which is also markedly dependent on thyroid hormone and growth hormone (GH) status. Here, we investigated how a 1-week exposure to the synthetic LXR agonist T0901317 affected GH secretion and thyroid hormone status in male rats. While the pulse frequency of GH secretion was marginally affected there was a highly significant decrease in the triiodo-L-thyronine/thyroxine (T3/T4) ratio in plasma. This effect was associated with decreased expression of deiodinase 1 (DIO1) and 2 (DIO2) mRNA in the liver and thyroid gland, respectively. Expression of sterol regulatory element binding protein-1c (SREBP-1c), the hallmark of stimulated lipogenesis, was markedly increased in both thyroid and pituitary implying that protracted pharmacological LXR activation may promote lipid accumulation in these endocrine tissues. These findings suggest that attention must be given to pituitary hormone dependent axes when developing therapeutic strategies based on agonism of the LXRs, e.g. for treatment of atherosclerosis.
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PMID:Effects of the synthetic liver X receptor agonist T0901317 on the growth hormone and thyroid hormone axes in male rats. 1847 93

Adiponectin is an adipocyte hormone that links visceral adiposity with insulin resistance and atherosclerosis. It is unique among adipocyte-derived hormones in that its circulating concentrations are inversely proportional to adiposity, and low adiponectin concentrations predict the development of type 2 diabetes and cardiovascular disease. Consequently, in the decade since its discovery, adiponectin has generated immense interest as a potential therapeutic target for the metabolic syndrome and diabetes. This review summarizes current research regarding the regulation of circulating adiponectin concentrations by physiological, pharmacological, and nutritional factors, with an emphasis on human studies. In humans, plasma adiponectin concentrations are influenced by age and gender, and are inversely proportional to visceral adiposity. In vitro studies suggest that adiponectin production may be determined primarily by adipocyte size and insulin sensitivity, with larger, insulin-resistant adipocytes producing less adiponectin. While adiponectin concentrations are unchanged after meal ingestion, they are increased by significant weight loss, such as after bariatric surgery. In addition, adiponectin production is inhibited by a number of hormones, including testosterone, prolactin, glucocorticoids and growth hormone, and by inflammation and oxidative stress in adipose tissue. Smoking decreases, while moderate alcohol consumption increases, circulating adiponectin concentrations. Dietary fatty acid composition in rodents influences adiponectin production via ligand-activated nuclear receptors (PPARs); however, current evidence in humans is equivocal. In addition to PPAR agonists (such as thiazolidinediones and fibrates), a number of pharmacological agents (angiotensin receptor type 1 blockers, ACE inhibitors, and cannabinoid receptor antagonists) used in treatment of the metabolic syndrome also increase adiponectin concentrations in humans.
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PMID:Physiological, pharmacological, and nutritional regulation of circulating adiponectin concentrations in humans. 1851 Apr 34

Ghrelin (Ghr), the natural ligand of growth hormone secretagogue receptor, is principally produced by the stomach. An interesting aspect in Ghr cardiovascular effects was elicited by the identification of ghrelin and GHS (growth hormone secretagogue) receptor mRNA expression in several cardiovascular tissues and cell types. In man, Ghr administration induced lowering of blood pressure, and decreased plasma levels were reported in several pathological conditions. The present investigation was performed to elucidate ghrelin effect on contraction and proliferation of human aortic smooth muscle cells (HASMC). Ghrelin receptor expression in HASMC was evaluated by RT-PCR, and binding studies were performed to elucidate the receptor kinetics. Ghr effect on angiotensin II-induced HASMC contraction and proliferation was evaluated in vitro. In addition, involvement of cAMP, ERK, and Akt pathways was investigated. PCR documented GHS-R1a expression. Binding of [(125)I-His(9)]-Ghrelin to HASMC was saturable in a dose-dependent manner. Scatchard analysis showed a single class of binding sites (Kd 1.58+/-0.23nM, B(max) 5848+/-291fmol/10(5) cells). In competition binding, (d-Lys(3))-GHRP-6 showed a capacity to compete with [(125)I-His(9)]-Ghrelin with Ki of 4.25nM. Ghrelin was able to inhibit angiotensin II-induced proliferation and contraction in a dose-response fashion via the cAMP/PKA pathway. Our data document that Ghr affects several HASMC functions, opening the way to consider ghrelin as a possible therapeutic target in many pathological conditions associated with vascular damage and remodelling.
Atherosclerosis 2009 Mar
PMID:Ghrelin inhibits contraction and proliferation of human aortic smooth muscle cells by cAMP/PKA pathway activation. 1866 2

This article describes the long time consequences of the isolated and lifetime growth hormone (GH) deficiency using a single model of GH releasing hormone resistance (GHRH) due to a homozygous mutation in the GHRH receptor gene, in a hundred of subjects. These consequences include severe short stature with final height between -9.6 and -5.2 standard deviations below of the mean, with proportional reductions of the bone dimensions; reduction of the anterior pituitary corrected to cranial volume and the thyroid, the uterus, the spleen and left ventricular mass volume, all corrected to body surface, in contrast of pancreas and liver size, bigger than in controls, when equally corrected. Body composition features included marked reduction in the amount of fat free mass (kg) and increase of fat mass percentage, with predominant abdominal deposit. In the metabolic aspects, we find increase in the total cholesterol and LDL cholesterol; reduction of the insulin and the insulin resistance assessed by Homeostasis model assessment; increase of ultra sensitive C reactive protein and systolic body pressure in adults, although without evidences of premature atherosclerosis. Other findings include smaller bone resistance, although above of the threshold of fractures, delayed puberty, normal fertility, small parity, anticipated climacteric and normal quality of life.
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PMID:[Long time consequences of the growth hormone deficiency]. 1879 80

Patients with growth hormone deficiency (GHD) are known to have reduced life expectancy due to increased cardiovascular and cerebrovascular events. An increase in asymmetric dimethylarginine (ADMA) levels previously found in GHD patients could promote premature atherosclerosis. The aim of this study was to determine whether 6-month growth hormone (GH) replacement therapy was able to decrease ADMA levels and ameliorate endothelial dysfunction. Thirty-one GHD patients were studied before and after 6 months of GH (4 microg/[kg d], daily) replacement therapy. Reduced pretreatment levels of serum insulin-like growth factor (IGF) 1 were normalized during GH treatment (88.2 +/- 62.5 to 191.7 +/- 80.3 ng/mL, P < .0001). After 6 months of GH replacement, plasma cyclic guanosine monophosphate levels significantly increased (2.14 +/- 0.52 to 3.54 +/- 1.2 ng/mL, P < .0001), serum ADMA levels were significantly decreased (0.65 +/- 0.1 vs 0.59 +/- 0.11 mumol/L, P < .05), and arganine (Arg) to ADMA ratio was significantly higher (155 +/- 53 vs 193 +/- 61, P < .01). No changes were observed for plasma nitric oxide end products (nitrite and nitrate) levels after GH treatment (21.9 +/- 14.9 vs 24.1 +/- 19.0 mumol/L, not significant). Basal forearm blood flow remained unchanged, whereas reactive hyperemia increased from 7.30 +/- 5.31 mL/100 mL forearm per minute before GH therapy to 13.18 +/- 7.30 mL/100 mL forearm per minute after 6 months of therapy (P < .001). There was a positive correlation between IGF-1 and cyclic guanosine monophosphate (r = 0.73, P < .0001), IGF-1 and reactive hyperemia (r = 0.63, P < .0001), and IGF-1 and Arg/ADMA ratio (r = 0.44, P < .01). Conversely, a negative correlation was found between IGF-1 and ADMA levels (r = -0.41, P < .02). At the end of the study period, fat-free mass, plasma glucose, and hemoglobin A(1c) levels significantly increased, even if they were still in the reference range, suggesting moderate alteration of glucose metabolism. In conclusion, in GHD patients, GH replacement contributes to decreased, to some extent, cardiovascular risk, reducing ADMA levels and improving Arg/ADMA ratio and endothelial dysfunction.
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PMID:Effects of growth hormone treatment on arginine to asymmetric dimethylarginine ratio and endothelial function in patients with growth hormone deficiency. 1901 91

Common chronic diseases of Western societies, such as coronary heart disease, diabetes mellitus, cancer, hypertension, obesity, dementia, and allergic diseases are significantly influenced by dietary habits. Cow's milk and dairy products are nutritional staples in most Western societies. Milk and dairy product consumption is recommended by most nutritional societies because of their beneficial effects for calcium uptake and bone mineralization and as a source of valuable protein. However, the adverse long-term effects of milk and milk protein consumption on human health have been neglected. A hypothesis is presented, showing for the first time that milk protein consumption is an essential adverse environmental factor promoting most chronic diseases of Western societies. Milk protein consumption induces postprandial hyperinsulinaemia and shifts the growth hormone/insulin-like growth factor-1 (IGF-1) axis to permanently increased IGF-1 serum levels. Insulin/IGF-1 signalling is involved in the regulation of fetal growth, T-cell maturation in the thymus, linear growth, pathogenesis of acne, atherosclerosis, diabetes mellitus, obesity, cancer and neurodegenerative diseases, thus affecting most chronic diseases of Western societies. Of special concern is the possibility that milk intake during pregnancy adversely affects the early fetal programming of the IGF-1 axis which will influence health risks later in life. An accumulated body of evidence for the adverse effects of cow's milk consumption from fetal life to childhood, adolescence, adulthood and senescence will be provided which strengthens the presented hypothesis.
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PMID:Milk--the promoter of chronic Western diseases. 1923 75

Consumption of cow's milk and cow's milk protein result in changes of the hormonal axis of insulin, growth hormone and insulin-like growth factor-1(IGF-1) in humans. Milk consumption raises IGF-1 serum levels in the perinatal period, adolescence and adulthood. During puberty with the physiological onset of increased secretion of growth hormone, IGF-1 serum levels increase and are further enhanced by milk consumption. IGF-1 is a potent mitogen; after binding to its receptor in various tissues, it induces cell proliferation and inhibits apoptosis. Keratinocytes and sebocytes, as well as the androgen-synthesizing adrenals and gonads, are stimulated by IGF-1. The epidemic incidence of adolescent acne in Western milk-consuming societies can be explained by the increased insulin- and IGF-1-stimulation of sebaceous glands mediated by milk consumption. Acne can be regarded as a model for chronic Western diseases with pathologically increased IGF-1-stimulation. Many other organs, such as the thymus, bones, all glands, and vascular smooth muscle cells as well as neurons are subject to this abnormally increased hormonal stimulation. The milk-induced change of the IGF-1-axis most likely contributes to the development of fetal macrosomia, induction of atopy, accelerated linear growth, atherosclerosis, carcinogenesis and neurodegenerative diseases. Observations of molecular biology are supported by epidemiologic data and unmask milk consumption as a promoter of chronic diseases of Western societies.
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PMID:Milk consumption: aggravating factor of acne and promoter of chronic diseases of Western societies. 1924 83

OBJECTIVE This study evaluated the influence of somatostatin receptor type 2 (SSTR2) polymorphisms on measures of glucose homeostasis in the Insulin Resistance Atherosclerosis Family Study (IRASFS). SSTR2 is a G-protein-coupled receptor that, in response to somatostatin, mediates inhibition of insulin, glucagon, and growth hormone release and thus may affect glucose homeostasis. RESEARCH DESIGN AND METHODS Ten single nucleotide polymorphisms (SNPs) spanning the gene were chosen using a SNP density selection algorithm and genotyped on 1,425 Hispanic-American individuals from 90 families in the IRASFS. These families comprised two samples (set 1 and set 2), which were analyzed individually and as a combined set. Single SNP tests of association were performed for four glucose homeostasis measures--insulin sensitivity (S(I)), acute insulin response (AIR), disposition index (DI), and fasting blood glucose (FBG)--using generalized estimating equations. RESULTS The SSTR2 locus was encompassed by a single linkage disequilibrium (LD) block (D' = 0.91-1.00; r(2) = 0.09-0.97) that contained four of the ten SNPs evaluated. Within the SSTR2-containing LD block, evidence of association was observed in each of the two sets and in a combined analysis with decreased S(I)(beta(homozygous) = -0.16; P(meta-analysis) = 0.0024-0.0030), decreased DI (beta(homozygous) = -0.35 to -5.16; P(meta-analysis) = 0.0075-0.027), and increased FBG (beta(homozygous) = 2.30; P(meta-analysis) = 0.045). SNPs outside the SSTR2-containing LD block were not associated with measures of glucose homeostasis. CONCLUSIONS We observed evidence for association of SSTR2 polymorphisms with measures of glucose homeostasis. Thus, variants in SSTR2 may influence pathways of S(I)to modulate glucose homeostasis.
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PMID:Association of SSTR2 polymorphisms and glucose homeostasis phenotypes: the Insulin Resistance Atherosclerosis Family Study. 1932 39

Blood pressure (BP) measurements provide information regarding risk factors associated with cardiovascular disease, but only in a specific artery. Arterial stiffness (AS) can be determined by measurement of arterial pulse wave velocity (APWV). Separate from any role as a surrogate marker, AS is an important determinant of pulse pressure, left ventricular function and coronary artery perfusion pressure. Proximal elastic arteries and peripheral muscular arteries respond differently to aging and to medication. Endogenous human growth hormone (hGH), secreted by the anterior pituitary, peaks during early adulthood, declining at 14% per decade. Levels of insulin-like growth factor-I (IGF-I) are at their peak during late adolescence and decline throughout adulthood, mirror imaging GH. Arterial endothelial dysfunction, an accepted cause of increased APWV in GH deficiency (GHD) is reversed by recombinant human (rh) GH therapy, favorably influencing the risk for atherogenesis. APWV is a noninvasive method for measuring atherosclerotic and hypertensive vascular changes increases with age and atherosclerosis leading to increased systolic blood pressure and increased left ventricular hypertrophy. Aerobic exercise training increases arterial compliance and reduces systolic blood pressure. Whole body arterial compliance is lowered in strength-trained individuals. Homocysteine and C-reactive protein are two inflammatory markers directly linked with arterial endothelial dysfunction. Reviews of GH in the somatopause have not been favorable and side effects of treatment have marred its use except in classical GHD. Is it possible that we should be assessing the combined effects of therapy with rhGH and rhIGF-I? Only multiple intervention studies will provide the answer.
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PMID:Arterial pulse wave velocity, inflammatory markers, pathological GH and IGF states, cardiovascular and cerebrovascular disease. 1933 49


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