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)

Post-heparin lipase activities were measured in normolipemic men with complaints suggestive of symptomatic coronary artery disease. A study group, who showed diffuse atherosclerotic narrowing of the coronary vessels, assessed by a quantitative computer-assisted analysis method, had a lowered hepatic lipase in comparison with a group with normal angiograms. Lipoprotein lipase was lower in the study group but well within the normal range and not statistically different. Some related hormones (cortisol, estradiol, testosterone and glucagon) were different in the two groups while others (insulin, human growth hormone, prolactin, thyroid hormones) were not. The results are discussed in view of the proposed role of hepatic lipase in the uptake of HDL-cholesterol by the liver.
Atherosclerosis 1983 Sep
PMID:Post-heparin lipases, lipids and related hormones in men undergoing coronary arteriography to assess atherosclerosis. 635 16

Vascular endothelial cells, serving as a barrier between vessel and blood, are exposed to shear stress in the body. Although endothelial responses to shear stress are important in physiological adaption to the hemodynamic environments, they can also contribute to pathological conditions--e.g., in atherosclerosis and reperfusion injury. We have previously shown that shear stress mediates a biphasic response of monocyte chemotactic protein 1 (MCP-1) gene expression in vascular endothelial cells and that the regulation is at the transcriptional level. These observations led us to functionally analyze the 550-bp promoter region of the MCP-1-encoding gene to define the cis element responding to shear stress. The shear stress/luciferase assay on the deletion constructs revealed that a 38-bp segment (-53 to -90 bp relative to the transcription initiation site) containing two divergent phorbol ester "12-O-tetradecanoylphorbol 13-acetate" (TPA)-responsive elements (TRE) is critical for shear inducibility. Site-specific mutations on these two sites further demonstrated that the proximal one (TGACTCC) but not the distal one (TCACTCA) was shear-responsive. Shear inducibility was lost after the mutation or deletion of the proximal site. This molecular mechanism of shear inducibility of the MCP-1 gene was functional in both the epithelial-like HeLa cells and bovine aortic endothelial cells (BAEC). In a construct with four copies of the TRE consensus sequences TGACTACA followed by the rat prolactin minimal promoter and luciferase gene, shear stress induced the reporter activities by 35-fold and 7-fold in HeLa cells and BAEC, respectively. The application of shear stress on BAEC also induced a rapid and transient phosphorylation of mitogen-activated protein kinases. Pretreatment of BAEC with TPA attenuated the shear-induced mitogen-activated protein kinase phosphorylation, suggesting that shear stress and TPA share a similar signal transduction pathway in activating cells. The present study provides a molecular basis for the transient induction of MCP-1 gene by shear stress.
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PMID:The cis-acting phorbol ester "12-O-tetradecanoylphorbol 13-acetate"-responsive element is involved in shear stress-induced monocyte chemotactic protein 1 gene expression. 764 39

Bromocriptine (BC), an ergot alkaloid with wide therapeutic use in humans, has been shown to inhibit proliferation of several abnormally hyperproliferative cells in vivo and in vitro. In the present study, direct effects of BC on mitogen-stimulated proliferation of rat vascular smooth muscle cells (VSMC) (A7r5 cells) and human aortic smooth muscle cells (HAOSMC) were examined in vitro. Twenty-four hour proliferative responses of quiescent A7r5 cells and HAOSMC to a variety of mitogens in the presence or absence of BC were determined by quantifying the incorporation of 3H-thymidine into DNA. BC at 1 microM inhibited the responses of A7r5 cells to various concentrations of fetal calf serum (FCS) by 50-70% without affecting the ED50 of FCS (2%). BC dose dependently inhibited the proliferation of A7r5 cells and HAOSMC stimulated by 2% FCS, with 52% inhibition at 1 and 0.1 microM, respectively. BC at 1 microM also completely inhibited the maximal mitogenic responses of A7r5 cells to prolactin, platelet-derived growth factor, insulin-like growth factor, and phorbol mysterate acetate (PMA), and BC at 1 microM completely inhibited the mitogenic response of HAOSMC to PMA. BC is a dopamine D2 agonist, a noradrenergic alpha 2 agonist, and an .alpha 1 antagonist, but the inhibitory effects of BC on A7r5 cell proliferation could not be mimicked by the specific D2 agonists, LY162502 and LY171555; the alpha 2 agonist, clonidine; or the alpha 1 antagonist, WB-4101. Neither dopamine nor the D2 agonist, LY162502, could inhibit HAOSMC proliferation induced by FCS. The PMA-induced stimulation of protein kinase C (PKC), a positive regulator of mitogenesis, could be completely blocked in A7r5 cells and HAOSMC by 1 and 0.1 microM BC, respectively. However, FPCS (2%)-induced activation of PKC in A7r5 cells and HAOSMC could only be blocked by 61 and 19% by BC (1 microM for A7r5 cells and 0.1 microM for HAOSMC), respectively. Given the existing evidence that BC reduces the severity of several other pathological conditions, such as insulin resistance, inflammation, and hyperlipidemia, which potentiate vascular disease, the current findings further suggest that BC use in the treatment of atherosclerosis and/or restenosis deserves further investigation.
Atherosclerosis 1997 Aug
PMID:Inhibitory effects of bromocriptine on vascular smooth muscle cell proliferation. 925 5

Estrogen treatment affects the hepatic synthesis and/or secretion of several proteins involved in clinically important pathological processes such as atherosclerosis, hypertension, and thrombosis. The endocrine regulation of the estrogen receptor (ER) concentration in primary cultures of rat hepatocytes was studied. Human growth hormone (hGH) and dexamethasone (DEX) in combination increased ER concentration 6-fold and ER mRNA levels 2.5-fold. These effects were not significantly different from those observed after treatment with the purely somatogenic bovine growth hormone (GH) in combination with DEX. Treatment with the lactogen ovine prolactin in the presence or absence of DEX did not significantly affect ER or ER mRNA concentrations. Triiodothyronine treatment at the most effective concentration (50 nM) increased ER and ER mRNA levels twofold. Medium supplementation with estradiol (0.1 nM) throughout the experiment did not affect the response to treatment with hGH and DEX. Treatment with high concentrations of ethinylestradiol in combination with hGH and DEX, however, increased the ER level twice as much as hGH and DEX without addition of estradiol or ethinylestradiol, whereas the ER mRNA concentration was the same in both the GH+DEX group and GH+ DEX+ (estradiol or ethinylestradiol) groups. These data indicate the importance of GH in combination with glucocorticoids for the maintenance of ER concentrations in the rat liver. Thyroid hormones may be of some, although minor importance, whereas the data suggest that prolactin is not directly involved in hepatic ER regulation.
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PMID:Hormonal regulation of the estrogen receptor in primary cultures of hepatocytes from female rats. 938 11

Stress has been linked to health problems such as atherosclerosis and prolonged wound healing, which involve the responses of injured endothelial cells. Though prolactin (PRL) levels become increased during the physiological response to stress, the significance and effects of these increases are largely unknown. Here we examined the effects of elevated, though physiological, concentrations of PRL on the responses of cultured endothelial cells after mechanical injury to cell monolayers. When treated at the time of injury with PRL levels of 62.5-1000 ng/mL, cells at the wound front became abnormal in shape and had reductions in f-actin staining in comparison to controls that were not PRL-treated. High PRL concentrations also inhibited the adhesion of cells to their growth surface in a dose-dependent manner. Using rhodamine-labeled PRL, we observed specific PRL uptake by these cells that suggested the presence of a PRL receptor. Finally, mRNA for the long form of the PRL receptor was detected by RT-PCR. To our knowledge, this is the first report demonstrating that (1) high PRL concentrations alter the actin cytoskeleton and adhesion of injured endothelial cells and (2) endothelial cells express the transcript for the PRL receptor. Thus, we report novel effects of PRL that may be mediated by activation of an endothelial cell PRL receptor.
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PMID:Structural and functional effects of high prolactin levels on injured endothelial cells: evidence for an endothelial prolactin receptor. 1105 Oct 45

Neuropeptide Y (NPY) is an important neurotransmitter in the central and peripheral nervous systems. It has a regulatory role in cardiovascular and metabolic functions and control of hormone release. The leucine 7 to proline 7 (Leu7Pro) polymorphism in the signal peptide of prepro-NPY is associated with increased blood lipid levels, accelerated atherosclerosis, and diabetic retinopathy. This study elucidated the role of this polymorphism in diurnal cardiovascular, metabolic, and hormonal functions of healthy subjects during rest. The two study groups comprised individuals with different genotype, but they were matched for age and body mass index. Subjects with the Leu7Pro polymorphism had significantly lower plasma NPY and norepinephrine concentrations, lower insulin concentrations, higher glucose concentrations, and lower insulin-glucose ratio in plasma than the controls. Heart rate was significantly higher during daytime in the subjects with Leu7Pro polymorphism. Furthermore, these subjects had significantly lower prolactin concentrations in plasma. Systolic and diastolic blood pressure, serum free fatty acid and plasma leptin, ACTH, cortisol, LH, FSH, TSH, free thyroxin, and melatonin concentrations were similar during the 24-h period, compared with controls. These results show that genetically determined changes in NPY levels lead to widespread consequences in the control of sympathoadrenal, metabolic, and hormonal balance in healthy subjects.
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PMID:Changes in diurnal sympathoadrenal balance and pituitary hormone secretion in subjects with Leu7Pro polymorphism in the prepro-neuropeptide Y. 1284 76

Platelet activation is involved in the pathogenesis of atherosclerosis and venous thromboembolism, and might therefore be a possible link between the two entities. Prolactin and leptin have recently been recognized as potent co-activators of ADP-dependent platelet aggregation or P-selectin expression, and are therefore suspected as additional risk factors for both arterial and venous thrombosis. There are clinical situations that have a known association with higher prolactin or leptin levels (pregnancy, obesity or anti-psychotic therapy) and increased risk of thromboembolic events. We compared the impact of both hormones on platelet activation in vitro and in vivo, indicating that prolactin has a stronger effect on platelet activation as leptin in vitro and in vivo. We have also demonstrated that prolactin levels are increased in so called idiopathic thrombosis, and that conversely, patients with prolactinoma have an increased frequency of thrombosis during the hyperprolactinemic state, in a retrospective analysis. Moreover, we have demonstrated increased prolactin values in stroke and myocardial infarction. Prospective studies have yet to be performed to give this theory its final confirmation. The involvement of hormonal factors in platelet aggregation and venous or arterial thrombosis may have important clinical implications such as for risk stratification of patients with venous and arterial thrombosis or new therapeutic options such as decreasing pro-coagulant hormone levels in certain risk situations.
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PMID:Co-activation of platelets by prolactin or leptin--pathophysiological findings and clinical implications. 1498 99

Hormones such as prolactin and leptin have recently been recognized as potent platelet aggregation co-activators, and have therefore been postulated as an additional risk factor for both arterial and venous thrombosis. Clinical situations exist that are known to be associated with higher leptin and/or prolactin levels (obesity, pregnancy, prolactinomas and anti-psychotic therapy respectively) and increased venous thrombosis or atherosclerosis risk. Therefore, we compared the impact of both hormones on platelet activation in vitro and in vivo. First, we investigated platelet aggregation and P-selectin expression after stimulation with 1,000 mU/l prolactin or 100 ng/ml leptin in five healthy volunteers in vitro. Prolactin revealed significant higher levels of P-selectin expression and platelet aggregation than leptin in all subjects. We also compared the correlation of prolactin and leptin values with the P-selection expression on platelets. Previously, we detected a significant correlation between prolactin values and ADP-stimulated P-selectin expression on platelets in pregnant women, patients with pituitary tumours, and patients on anti-psychotic therapy. In contrast, leptin did not correlate with P-selectin expression in all subject groups investigated. However, leptin correlated with body mass index in the subjects investigated. Our data indicate that prolactin has a stronger effect on platelet activation as leptin in vitro and in vivo. Moreover, our data suggest that the stronger effect of prolactin on ADP-stimulated platelet aggregation, compared to leptin, depends on higher stimulation of CD62p expression by prolactin.
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PMID:Differences in platelet activation by prolactin and leptin. 1530 27

Adiponectin is an adipocyte-derived hormone involved in glucose, lipid and energy metabolism. A low plasma adiponectin concentration is associated with insulin resistance, obesity and atherosclerosis. In women, energy homeostasis is remarkably changed during gestation and lactation in order to supply sufficient nutrition for a fetus or newborn. In this study we aimed to elucidate the physiological impact of gestation and lactation on the plasma adiponectin levels and the influence of reproduction-related hormones on adiponectin secretion. We studied the longitudinal changes in plasma adiponectin concentration during pregnancy (1st, 2nd and 3rd trimester) and lactation (3 days and 1 month after the delivery) in lean healthy women (n = 22). The plasma adiponectin level declined slightly as the pregnancy advanced and reached its lowest level during lactation (12.25 +/- 0.182 microg/ml at early pregnancy vs. 6.88 +/- 0.375 microg/ml at 3 days postpartum, p < 0.001). In order to investigate the role of the lactogenic hormone prolactin in the decrease of plasma adiponectin levels during lactation, we further performed in vitro experiments using human primary cultured adipocytes. Western blotting of the adipocyte lysate and ELISA of the culture medium revealed that exogenous prolactin inhibited both production and secretion of adiponectin in a dose-dependent manner. Our results thus suggests that prolactin affects the regulation of maternal metabolism through suppression of adiponectin.
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PMID:Hypoadiponectinemia in lean lactating women: Prolactin inhibits adiponectin secretion from human adipocytes. 1684 35

Adiponectin is an adipocyte-derived hormone involved in the regulation of carbohydrate and lipid metabolism. Its concentrations are decreased in patients with obesity, type 2 diabetes and atherosclerosis and are higher in females than in males. Gender differences of adiponectin levels raise the possibility that sex hormones directly regulate its serum concentrations, which may in turn influence insulin sensitivity in different phases of the menstrual cycle. To test this hypothesis we measured serum adiponectin, estradiol, progesterone, luteinizing hormone and follicle-stimulating hormone concentrations daily throughout the menstrual cycle in six healthy women. Mean adiponectin levels strongly positively correlated with serum cortisol concentrations [R=0.94286; p=0.0048 (Spearman correlation test)], but were not significantly related to other anthropometric, biochemical and hormonal characteristics of the subjects (BMI, blood glucose, insulin, testosterone, prolactin, cholesterol, HDL cholesterol, LDL cholesterol, triglycerides concentrations, or atherogenic index). Furthermore, no significant changes of serum adiponectin levels were found throughout the menstrual cycle. We conclude that changes in sex hormones during the menstrual cycle do not affect total circulating adiponectin levels in healthy women. Therefore, the differences in insulin sensitivity in various phases of the menstrual cycle are not due to changes of circulating adiponectin levels.
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PMID:The influence of hormonal changes during menstrual cycle on serum adiponectin concentrations in healthy women. 1717 33


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