Home About us Contact
|
Home About us Contact | ||
|
|
||
Human Arteries (human + artery)
Selected AbstractsHLA Class I Antibodies Provoke Graft Arteriosclerosis in Human Arteries Transplanted into SCID/Beige MiceAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009S. Galvani Antibodies toward HLA class I and/or MICA are commonly observed in transplanted patients suffering from allograft arteriosclerosis, also called chronic vascular rejection (CVR). The relative importance of cellular versus humoral alloreactivity for CVR is still disputed. We demonstrate that antibodies toward HLA class I provoke lesions typical for CVR in human arteries in vivo in the absence of cellular immunity. To show this, we grafted segments of human mesenteric arteries from 8 deceased organ donors into 36 immunodeficient SCID/beige mice in the infrarenal aortic position. Three mice died postoperatively. The remaining 33 mice received weekly i.v. injections of either a monoclonal antibody toward HLA class I, toward MICA or an irrelevant monoclonal antibody. At sacrifice after 6 weeks, mice receiving the HLA antibody showed a significant neointimal thickening in the grafted artery due to smooth muscle cell (SMC) proliferation while control mice receiving anti-MICA or irrelevant antibody showed little or no thickening. Whereas antibodies toward HLA class I were mitogenic to SMC in vitro, those directed toward MICA did not have any effect. Humoral alloreactivity toward HLA may thus play a causal role for the development of CVR and this opens new possibilities for the treatment of CVR. [source] Recruitment of CXCR3+ and CCR5+ T Cells and Production of Interferon-,-Inducible Chemokines in Rejecting Human ArteriesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2005William R. Burns Chemokine receptors preferentially expressed by Th1 cells and their IFN-,-inducible ligands predominate in experimental and clinical allograft rejection. Previous chemokine-related transplantation studies have focused on parenchymal and microvascular inflammation which are of importance in acute rejection, but are not necessarily relevant in immune-mediated injury of conduit arteries. We have recently described a model of progressive human T cell-mediated infiltration and injury of allogeneic coronary artery segments using immunodeficient mouse hosts. In the present study, we investigated if recruitment of allogeneic T cells to different vascular compartments correlated with the expression of chemokines and their receptors. Transcripts were quantified by laser capture microdissection/real-time RT-PCR and their distribution was correlated to the corresponding protein expression detected by immunohistochemistry. Infiltrating T cells, confined to the adventitia and intima, expressed CXCR3 and CCR5, but were not recruited into the media despite production by vascular smooth muscle cells of IP-10, Mig, I-TAC, RANTES and MIP-1,. Chemokine mRNA was detected primarily in vascular cells, although chemokine protein largely localized to infiltrating leukocytes which uniquely expressed their cognate receptors. These data explain the recruitment of IFN-,-secreting T cells to the vessel wall, and reinforce the suggestion that the arterial media may be a site of immunological privilege. [source] Comparison of the contractile responses of human coronary bypass grafts and monkey arteries to human urotensin-IIFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2001J. Paysant Human urotensin-II (hU-II) is a cyclic peptide recently cloned in humans and present in human cardiac tissue and human arteries. The effects of hU-II were studied on human coronary bypass grafts in vitro. In three out of eight human mammary arteries, and two out of three human radial arteries, hU-II caused contraction; human saphenous veins did not respond to hU-II. When it exists, the contraction slowly develops and has a low-to-moderate intensity. All radial arteries obtained from young healthy non-human primates contracted strongly to hU-II. [source] Pharmacology of the Selective 5-HT1B/1D Agonist FrovatriptanHEADACHE, Issue 2002M.B. Comer BSc Objective.,To determine the pharmacological profile of frovatriptan. Background.,Frovatriptan is a new 5-HT1B/1D agonist developed for the treatment of migraine. Methods.,Pharmacological studies were performed using in vitro and in vivo techniques. Results.,Radioligand-binding studies showed that frovatriptan has a high affinity for 5-HT1B and 5-HT1D receptors, and moderate affinity for 5-HT1A, 5-HT1F, and 5-HT7 receptors. In vitro, frovatriptan acts as a potent full agonist at human cloned 5-HT1B and 5-HT1D receptors, and as a moderately potent full agonist at 5-HT7 receptors. Studies of frovatriptan in isolated human arteries demonstrated a lower threshold for constriction of cerebral than coronary vasculature and a bell-shaped dose-response curve was apparent in the coronary arteries. In anesthetized dogs, frovatriptan administration produced no measurable effect on cardiac function or on blood pressure. Frovatriptan had no effects on coronary blood flow following transient coronary artery occlusion, whereas sumatriptan produced a prolonged and significant decrease in coronary blood flow. Conclusion.,The pharmacology of frovatriptan suggests that it should be an effective agent for the acute treatment of migraine, with a low potential for undesirable peripheral effects. [source] HLA Class I Antibodies Provoke Graft Arteriosclerosis in Human Arteries Transplanted into SCID/Beige MiceAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009S. Galvani Antibodies toward HLA class I and/or MICA are commonly observed in transplanted patients suffering from allograft arteriosclerosis, also called chronic vascular rejection (CVR). The relative importance of cellular versus humoral alloreactivity for CVR is still disputed. We demonstrate that antibodies toward HLA class I provoke lesions typical for CVR in human arteries in vivo in the absence of cellular immunity. To show this, we grafted segments of human mesenteric arteries from 8 deceased organ donors into 36 immunodeficient SCID/beige mice in the infrarenal aortic position. Three mice died postoperatively. The remaining 33 mice received weekly i.v. injections of either a monoclonal antibody toward HLA class I, toward MICA or an irrelevant monoclonal antibody. At sacrifice after 6 weeks, mice receiving the HLA antibody showed a significant neointimal thickening in the grafted artery due to smooth muscle cell (SMC) proliferation while control mice receiving anti-MICA or irrelevant antibody showed little or no thickening. Whereas antibodies toward HLA class I were mitogenic to SMC in vitro, those directed toward MICA did not have any effect. Humoral alloreactivity toward HLA may thus play a causal role for the development of CVR and this opens new possibilities for the treatment of CVR. [source] Effects of potassium channel opener KRN4884 on human conduit arteries used as coronary bypass graftsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2000Zhen Ren Aims The effects of a new potassium channel opener KRN4884 on human arteries have not been studied. This study was designed to investigate the effects of KRN4884 on the human internal mammary artery (IMA) in order to provide information on possible clinical applications of KRN4884 for preventing and relieving vasospasm of arterial grafts in coronary artery bypass grafting. Methods IMA segments (n = 140) taken from patients undergoing coronary surgery were studied in the organ chamber. Concentration-relaxation curves for KRN4884 were established in the IMA precontracted with noradrenaline (NA), 5-hydroxytryptamine (5-HT), angiotensin II (ANG II), and endothelin-1 (ET-1). The effect of glibenclamide (GBC) on the KRN4884-induced relaxation was also examined in NA or 5-HT-precontracted IMA. Concentration-contraction curves for the four vasoconstrictors were constructed without/with pretreatment of KNR4884 (1 or 30 µm) for 15 min. Results KRN4884 induced less relaxation (P < 0.05) in the precontraction induced by ET-1 (72.9 ± 5.5%) than by ANG II (94.2 ± 3.2%) or NA (93.7 ± 4.1%) with lower EC50 (P < 0.05) for ANG II (,8.54 ± 0.54 log m) than that for NA (,6.14 ± 0.15 log M) or ET-1 (,6.69 ± 0.34 log m). The relaxation in the IMA pretreated with GBC was less than that in control (P < 0.05). KRN4884-pretreatment significantly reduced the contraction (P < 0.05) induced by NA (151.3 ± 18.4% vs 82.7 ± 8.7%), 5-HT (82.7 ± 12.2% vs 30.1 ± 7.3%), and ANG II (24.3 ± 6.3% vs 5.4 ± 1.6%), but did not significantly reduce the contraction induced by ET-1 (P > 0.05). Conclusion KRN4884 has marked vasorelaxant effects on the human IMA contracted by a variety of vasoconstrictors and the effect is vasoconstrictor-selective. [source] Differential effects of glucose on agonist-induced relaxations in human mesenteric and subcutaneous arteriesBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2008A MacKenzie Background and purpose: Acute periods of hyperglycaemia are strongly associated with vascular disorder, yet the specific effects of high glucose on human blood vessel function are not fully understood. In this study we (1) characterized the endothelial-dependent relaxation of two similarly sized but anatomically distinct human arteries to two different agonists and (2) determined how these responses are modified by acute exposure to high glucose. Experimental approach: Ring segments of human mesenteric and subcutaneous arteries were mounted in a wire myograph. Relaxations to acetylcholine and bradykinin were determined in a control (5 mM) and high glucose (20 mM) environment over a 2 and 6 h incubation period. Key results: Bradykinin-induced relaxation in both sets of vessels was mediated entirely by EDHF whilst that generated by acetylcholine, though principally generated by EDHF, also had contribution from prostacyclin and possibly nitric oxide in mesenteric and subcutaneous vessels, respectively. A 2-h incubation of high glucose impaired bradykinin-induced relaxation of subcutaneous vessels whilst, in contrast, the relaxation generated by bradykinin in mesenteric vessels was enhanced at the same time point. High glucose significantly augmented the relaxation generated by acetylcholine in mesenteric and subcutaneous vessels at a 2 and 6 h incubation point, respectively. Conclusions and implications: Short periods of high glucose exert a variable influence on endothelial function in human isolated blood vessels that is dependent on factors of time, agonist-used and vessel studied. This has implications for how we view the effects of acute hyperglycaemia found in patients with diabetes mellitus as well as other conditions. British Journal of Pharmacology (2008) 153, 480,487; doi:10.1038/sj.bjp.0707592; published online 26 November 2007 [source] Vasoconstrictor activity of novel endothelin peptide, ET-1(1 , 31), in human mammary and coronary arteries in vitroBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2001Janet J Maguire The ability of the putative chymase product of big endothelin-1 (big ET-1), ET-1(1 , 31), to constrict isolated endothelium-denuded preparations of human coronary and internal mammary artery was determined. pD2 values in coronary and mammary artery respectively were 8.21±0.12 (n=14) and 8.55±0.11 (n=12) for ET-1, 6.74±0.11 (n=16) and 7.10±0.08 (n=16) for ET-1(1 , 31) and 6.92±0.10 (n=15) and 7.23±0.11 (n=12) for big ET-1. ET-1(1 , 31) was significantly less potent than ET-1 (P<0.001, Student's t -test) and equipotent with big ET-1. Vasoconstrictor responses to 100 , 700 nM ET-1(1 , 31) were significantly (P<0.05, Student's paired t -test) attenuated by the ETA antagonist PD156707 (100 nM). There was no effect of the ECE inhibitor PD159790 (30 ,M), the ECE/NEP inhibitor phosphoramidon (100 ,M) or the serine protease inhibitor chymostatin (100 ,M) on ET-1(1 , 31) responses in either artery. Radioimmunoassay detected significant levels of mature ET in the bathing medium of coronary (1.6±0.5 nM, n=14) and mammary (2.1±0.6 nM, n=14) arteries, suggesting that conversion of ET-1(1 , 31) to ET-1 contributed to the observed vasoconstriction. ET-1(1 , 31) competed for specific [125I]-ET-1 binding to ETA and ETB receptors in human left ventricle with a pooled KD of 71.6±7.0 nM (n=3). Therefore, in human arteries the novel peptide ET-1(1 , 31) mediated vasoconstriction via activation of the ETA receptor. The conversion of ET-1(1 , 31) to ET-1, by an as yet unidentified protease, must contribute wholly or partly to the observed constrictor response. Chymase generated ET-1(1 , 31) may therefore represent an alternative precursor for ET-1 production in the human vasculature. British Journal of Pharmacology (2001) 134, 1360,1366; doi:10.1038/sj.bjp.0704384 [source] | ||||||||||