UMLS:C0004153 - FACTA Search

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)

Experience of application of alprostan (PGE1, alprostadil) in 19 patients with atherosclerotic affection of vessels, chronic and acute ischemia of lower extremities in III-IV stage in combination with affection of other vascular basins was summarized. In 10 patients, to whom operative vascular reconstruction was contraindicated and/or technically unrealizable, the conservative treatment was conducted using alprostan during 12-25 days up to the clinical effect achievement (total dose up to 1.6 mg). In 9 patients after performance of conservative treatment using alprostan the vascular bed reconstruction was done. Daily infusion of alprostan in 0.1 mg dose diluted in 250-400 ml of isotonic solution of sodium chloride during 2.5-3 h with duration of course not less than 15 days and 1.2-2.2 mg total dose of preparation constitutes an optimal scheme of treatment. Good result was noted in treatment of patients in stage II of ischemia, application of alprostan in stage IV of ischemia had permitted to reduce the extremity amputation volume or to escape it on the whole, and to restore more rapidly the cutaneous integrity in the trophic disorders regions. The alprostan usage is trustworthy in patients with multifocal atherosclerosis with the cardiac coronary vessels affection in an ischemic heart disease.
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PMID:[Clinical efficacy of alprostan in treatment of obliterating multifocal atherosclerotic affection of arteries in patients with critical ischemia of lower extremities]. 1150 31

Transforming growth factor beta1 (TGFbeta1) is a multifunctional growth factor involved in immune function, atherosclerosis, fibrotic disease, diabetic complications and bone turnover. It is synthesized in large quantities by bone cells in response to hormones and mechanical stimuli. Plasma contains inactive "latent" TGFbeta1, which consists of the precursor molecule and a TGFbeta1-binding protein. Platelets store latent TGFbeta1 in their alpha-granules, and serum therefore contains large amounts of latent TGFbeta1. We developed a technique for determining latent plasma TGFbeta1 and investigated whether circulating TGFbeta1 is affected by the stimulation of bone formation in response to strength training. Ten healthy students with low training activity participated in a heavy exercise programme over 4 weeks. Blood was drawn into citrate-filled syringes containing prostaglandin E(1) (PGE(1)) and immediately centrifuged at 4 degrees C. TGFbeta1 was determined with a sandwich ELISA standardized with National Institute for Biological Standards and Controls (NIBSC) materials. Six of the ten students completed the training. Highly reproducible values (500-600 pg/ml) of latent TGFbeta1 in plasma were determined. Baseline levels of TGFbeta1 were 525 (50) pg/ml [mean (SE)], which is in the range observed for young adults. TGFbeta1 concentrations rose significantly to 710 (65) pg/ml after 2 weeks of training and thereafter slowly declined to 650 (62) pg/ml after 2 weeks and 440 (33) pg/ml after 4 weeks, respectively. No active TGFbeta1 was detectable in citrate PGE1 plasma samples. Serum levels were between 6000 and 10,000 pg/ml and contained 200-400 pg/ml active TGFbeta1. In contrast to previous reports, plasma did not contain measurable amounts of circulating active TGFbeta1. We demonstrate that heavy exercise transiently elevates latent TGFbeta1 concentrations in plasma. TGFbeta1 is produced by osteoblasts in considerable amounts; therefore, we assume that the observed changes are partly due to enhanced TGFbeta1 production or release in bone, since the quantities of TGFbeta1 produced by other cells are comparably small.
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PMID:Circulating transforming growth factor beta1 (TGFbeta1) is elevated by extensive exercise. 1188 26

Sexual dysfunction is defined as "disturbances in sexual desire and in the psychophysiological changes that characterize the sexual response cycle and cause marked distress and interpersonal difficulty". The female sexual response cycle consists of three phases: desire, arousal, and orgasm. Various organs of the external and internal genitalia, e.g. vagina, clitoris, labia minora, vestibular bulbs, pelvic floor muscles and uterus, contribute to female sexual function. During sexual arousal, genital blood flow and sensation are increased. The vaginal canal is moistened (lubrication). During orgasm, there is rhythmical contraction of the uterus and pelvic floor muscles. Within the central nervous system, hypothalamic, limbic-hippocampal structures play a central role for sexual arousal. Sexual arousal largely depends on the sympathetic nervous system. Moreover, nonadrenergic/noncholinergic neurotransmitters (NANC), e.g. vasoactive intestinal polypeptide (VIP) and nitric oxide (NO), are involved in smooth muscle relaxation and enhancement of genital blood flow. Furthermore, various hormones may influence female sexual function. Estrogen has a significant role in maintaining vaginal mucosal epithelium as well as sensory thresholds and genital blood flow. Androgens primarily affect sexual desire, arousal, orgasm and the overall sense of well-being. The internationally accepted classification of female sexual dysfunction consists of hypoactive sexual desire disorders, sexual aversion disorders, sexual arousal disorders, orgasmic disorders and sexual pain disorders. Vascular insufficiency, e.g. due to atherosclerosis, and neurologic diseases, e.g. diabetic neuropathy, are major causes of sexual dysfunction. Additionally, sexual dysfunction may be due to changes in hormonal levels, medications with sexual side effects or of psychological origin. For the diagnosis of female sexual dysfunction, a detailed history should be taken initially, followed by a physical examination and laboratory studies. Physiologic monitoring of parameters of arousal potentially allows to diagnose organic diseases. Recordings at baseline and following sexual stimulation are recommended to determine pathologic changes that occur with arousal. Duplex Doppler sonography, photoplethysmography or the measurement of vaginal and minor labial oxygen tension may help to evaluate genital blood flow. Moreover, measurements of vaginal pH and compliance should be performed. Neurophysiological examination, e.g. measurement of the bulbocavernosus reflex and pudendal evoked potentials, genital sympathetic skin response (SSR), warm, cold and vibratory perception thresholds as well as testing of the pressure and touch sensitivity of the external genitalia, should be performed to evaluate neurogenic etiologies. Medical management of female sexual dysfunction so far is primarily based on hormone replacement therapy. Application of estrogen results in decreased pain and burning during intercourse. The efficacy of various other medications, e.g. sildenafil, L-arginine, yohimbine, phentolamine, apomorphine and prostaglandin E1, in the treatment of female sexual dysfunction is still under investigation.
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PMID:[Female sexual dysfunction: a systematic overview of classification, pathophysiology, diagnosis and treatment]. 1588 Sep 11

Since endothelial damage is a trigger for the progression of atherosclerosis, we evaluated the clinical utility of prostaglandin E1 (PGE1) in relation to peripheral blood flow and regulation of hepatocyte growth factor (HGF), an angiogenic growth factor, in patients with peripheral arterial disease (PAD). Fourteen male patients with PAD who showed the characteristic symptoms of arteriosclerosis obliterans (Fontaine I: n=2; Fontaine II: n=4; Fontaine III: n=2; Fontaine IV: n=6), confirmed by angiography, were enrolled in this study. Patients were administrated synthetic PGE1 at a dose of 120 microg per day for 14 consecutive days. Measurement of peripheral blood flow and serum HGF concentration was performed before PGE1 treatment and after 14 days of administration. Interestingly, intravenous administration of PGE1 for 2 weeks significantly increased the blood flow as assessed by a laser Doppler imager (p<0.01). In patients with Fontaine III and IV, serum HGF concentration was significantly higher than that in patients with Fontaine I or II and normal subjects. Of importance, administration of PGE1 further increased serum HGF concentration as compared to that before treatment (p<0.01). The increase in circulating HGF might work as a compensatory mechanism to decrease local HGF expression in patients with PAD, since HGF acts as an angiogenic growth factor with anti-apoptotic actions on endothelial cells. Moreover, to confirm the stimulatory effect of PGE1 on HGF in vessels, we employed an in vitro culture system. PGE1 increased HGF production and the growth of human cultured vascular endothelial cells. The stimulatory effect of PGE1 on HGF production might be due to an increase in cAMP, since forskolin and 8-bromo-cAMP induced HGF production. In conclusion, we demonstrated that administration of PGE1 stimulated peripheral blood flow, accompanied by an increase in systemic HGF concentration. Also, our in vitro data suggested that PGE1 augmented not only the systemic HGF level, but also local HGF production, probably through cAMP accumulation, resulting in improvement of endothelial function and blood flow.
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PMID:Increase in peripheral blood flow by intravenous administration of prostaglandin E1 in patients with peripheral arterial disease, accompanied by up-regulation of hepatocyte growth factor. 1500 71

Selective COX-2 inhibitors increase the risk of myocardial infarction and stroke. This has been attributed to their ability to inhibit endothelial COX-2 derived prostacyclin (PGI2) but not platelet COX-1 derived thromboxane A2 (TXA2). On the other hand, aspirin blocks both COX-1 and COX-2 enzymes without decreasing PGI2 but blocks TXA2 synthesis that explains its beneficial action in the prevention of coronary heart disease (CHD). The inhibitory action of aspirin on COX-1 and COX-2 enzymes enhances the tissue concentrations of dihomo-gamma-linolenic acid (DGLA), arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). These fatty acids form precursors to PGE1, PGI2, PGI3, lipoxins (LXs), and resolvins that have anti-inflammatory actions. In contrast, increase in the concentrations of DGLA, AA, EPA, and DHA is much less with specific COX-2 inhibitors since they do not block the formation of eicosanoids through COX-1 pathway. COX-2 inhibitors interfere with the formation of LXs and resolvins that have neuroprotective and cardioprotective actions. EPA and PGI2 have anti-arrhythmic action. EPA, DHA, and AA augment eNO formation that prevents atherosclerosis. This suggests that COX-2 inhibitors increase cardiovascular and stroke risk by interfering with the formation of eNO, PGI2, LXs, and resolvins and implies that combining EFAs with COX-2 inhibitors could prevent these complications.
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PMID:Can COX-2 inhibitor-induced increase in cardiovascular disease risk be modified by essential fatty acids? 1619 Jan 33

Atherosclerosis is a dynamic process. Dyslipidemia, diabetes mellitus, hypertension, obesity, and shear stress of blood flow, the risk factors for the development of atherosclerosis, are characterized by abnormalities in the metabolism of essential fatty acids (EFAs). Gene expression profiling studies revealed that at the sites of atheroslcerosis-prone regions, endothelial cells showed upregulation of pro-inflammatory genes as well as antioxidant genes, and endothelial cells themselves showed changes in cell shape and proliferation. Uncoupled respiration (UCP-1) precedes atherosclerosis at lesion-prone sites but not at the sites that are resistant to atherosclerosis. UCP-1 expression in aortic smooth muscle cells causes hypertension, enhanced superoxide anion production and decreased the availability of NO, suggesting that inefficient metabolism in blood vessels causes atherosclerosis without affecting cholesterol levels. Thus, mitochondrial dysfunction triggers atherosclerosis. Atherosclerosis-free aortae have abundant concentrations of the EFA-linoleate, whereas fatty streaks (an early stage of atherosclerosis) are deficient in EFAs. EFA deficiency promotes respiratory uncoupling and atherosclerosis. I propose that a defect in the activity of Delta6 and Delta5 desaturases decreases the formation of gamma-linolenic acid (GLA), dihomo-DGLA (DGLA), arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) from dietary linoleic acid (LA) and alpha-linolenic acid (ALA). This, in turn, leads to inadequate formation of prostaglandin E1 (PGE1), prostacyclin (PGI2), PGI3, lipoxins (LXs), resolvins, neuroprotectin D1 (NPD1), NO, and nitrolipids that have anti-inflammatory and platelet anti-aggregatory actions, inhibit leukocyte activation and augment wound healing and resolve inflammation and thus, lead to the initiation and progression atheroslcerosis. In view of this, it is suggested that Delta6 and Delta5 desaturases could serve as biological target(s) for the discovery and development of pharmaceuticals to treat atherosclerosis.
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PMID:A defect in the activity of Delta6 and Delta5 desaturases may be a factor in the initiation and progression of atherosclerosis. 1746 97

Neointimal cushion formation (NCF) is an important vascular remodeling for anatomical closure of the ductus arteriosus (DA). Inflammatory responses to vascular injury or atherosclerosis are known to be associated with the pathogenesis of NCF. We found that the expression of interleukin (IL)-15 mRNA was significantly higher in rat DA than in the aorta. IL-15 immunoreactivity was detected predominantly in the internal elastic laminae (IEL) and to a lesser extent in smooth muscle cells (SMCs) in rat DA. Prostaglandin E (PGE) increased the expression of IL-15 mRNA in cultured DA SMCs. IL-15 significantly attenuated the platelet-derived growth factor (PDGF)-BB-mediated SMC proliferation, but did not change SMC migration. IL-15 significantly attenuated PGE1-induced hyaluronic acid (HA) production in a dose-dependent manner, which is a potent stimulator of NCF. Accordingly, IL-15 might have an inhibitory effect on the physiologic vascular remodeling processes in closing the DA.
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PMID:Interleukin-15 inhibits smooth muscle cell proliferation and hyaluronan production in rat ductus arteriosus. 1766 61

The results of examination, surgical treatment and prophylaxis of infection complications were analyzed in 219 patients, suffering abdominal aorta and peripheral arteries obliterating atherosclerosis in a stage of critical ischemia of the lower extremities tissues (CILE), of them in 22 (10.1%) diabetes mellitus was diagnosed. There was established the importance of studying of regional blood flow and microcirculation state. Complex treatment of abdominal aorta and peripheral arteries obliterating atherosclerosis, including surgical intervention and infusion therapy, using prostaglandin E1, had permitted to eliminate CILE more than in 91% patients. The necessity of complex prophylaxis of purulent complications in reconstructive operations, using antibiotics and immunocorrectors, was proved.
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PMID:[Diagnosis and treatment of chronic critical ischemia of the lower extremity tissues]. 1927 32

Erectile dysfunction (ED) is observed in up to 81% of men with systemic sclerosis (SSc) and therefore should be counselled as a common complaint in this disorder. Whereas ED is frequently associated with atherosclerosis in the general population in which it is also a harbinger of cardiovascular events, ED has a different aetiology in SSc. In SSc the penile blood flow is impaired due to both myointimal proliferation of small arteries and corporal fibrosis. Data on the prevention of ED in SSc are not available. On-demand phosphodiesterase type 5 (PDE-5) inhibitors are not effective in improving erectile function, but fixed daily or alternate day regimens of long acting PDE-5 inhibitors provide a measurable, although often limited, clinical benefit. When intracavernous injections of prostaglandin E1 (alprostadil) are ineffective, the implantation of a penile prosthesis may be considered. Complex treatment options may require the involvement of urology.
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PMID:Erectile dysfunction in systemic sclerosis. 1952 6

Activated platelets release a wide range of inflammatory mediators, including members of the tumour necrosis factor (TNF) superfamily (e.g. CD40 ligand [CD40L] and LIGHT). Such platelet-mediated inflammation could be involved in atherogenesis and plaque destabilisation. In the present study we investigated whether APRIL, another member of the TNF superfamily that has been detected in megakaryocytes, could be released from platelets upon activation. The release of APRIL was studied in thrombin receptor (SFLLRN) activated platelets, and the expression of APRIL was examined in plasma and within the atherosclerotic lesion in patients with carotid and coronary atherosclerosis. Upon SFLLRN activation, there was a gradual release of APRIL, reaching maximum after 90 minutes. While this pattern is similar to that of CD40L and LIGHT, the release of APRIL was quite differently regulated. Thus, prostaglandin E1, but not inhibitors of metal-dependent proteases and actin polymerisation or the lack of GP IIb/IIIa, blocks APRIL release in activated platelets. With relevance to atherogenesis, we found that patients with coronary artery disease (n=80) had raised plasma levels of APRIL as compared with controls (n=20), and APRIL immunoreactivity was detected in aggregated platelets within the ruptured plaque in patients with myocardial infarction and within macrophages in symptomatic carotid plaques. In conclusion, activated platelets release significant amounts of APRIL in a long-lasting manner, differently regulated than the gradual release of other platelet-derived TNF superfamily ligands. The enhanced expression of APRIL in atherosclerotic disorders, both systemically and within the lesion, may suggest a potential involvement of APRIL in atherogenesis.
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PMID:The tumour necrosis factor superfamily ligand APRIL (TNFSF13) is released upon platelet activation and expressed in atherosclerosis. 1980 56

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