• complexes
  • Immunoblotting analysis of the conditioned media obtained from monolayers of HUVECs treated with increasing concentrations of t-PA (less than or equal to 10 micrograms/ml) revealed a dose-dependent formation of both t-PA/PAI-1 complexes, and of a 42,000-Mr cleaved or modified form of the inhibitor. (rupress.org)
  • 3 Aliskiren was synthesized using both crystal structure analysis of renin inhibitor complexes and computational molecular modeling with the intent of addressing issues of solubility and affinity. (ahajournals.org)
  • coagulation
  • The adherent platelets recruit and activate monocytes, which start releasing chemokines, cytokines and enzymes that degrade the endothelial matrix and trigger expression of tissue factor, the main activator of the coagulation cascade. (haematologica.org)
  • It is known that HRG binds heme, dyes, and divalent metal ions and it is thought to have multiple roles in the human blood, including roles in immunity, angiogenesis and coagulation. (wikipedia.org)
  • It also may enhance coagulation by inhibiting the function of tissue factor pathway inhibitor. (wikipedia.org)
  • enzyme
  • Theoretically, complete suppression of RAAS by renin inhibition has broad applicability in disease states associated with excess activation of the RAAS and continued production of angiotensin II (Ang II) despite angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) therapy. (ahajournals.org)
  • Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin. (abcam.com)
  • Although most serpins control proteolytic cascades, some proteins with a serpin structure are not enzyme inhibitors, but instead perform diverse functions such as storage (as in egg white-ovalbumin), transport as in hormone carriage proteins (thyroxine-binding globulin, cortisol-binding globulin) and molecular chaperoning (HSP47). (wikipedia.org)
  • reductase inhibitors
  • Objective- 3-Hydroxyl-3-methyl coenzyme A reductase inhibitors (statins) can function to protect the vasculature in a manner that is independent of their lipid-lowering activity. (ahajournals.org)
  • From a clinical perspective, large prospective trials with 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors or statins suggest that these agents may have beneficial effects in cardiovascular disease in addition to their cholesterol-lowering effects. (ahajournals.org)
  • vascular
  • 1 Upon plaque rupture, platelets adhere to the vascular lesion providing a procoagulant surface that starts thrombin formation and systemic platelet activation. (haematologica.org)
  • Tumor necrosis factor-alpha stimulates ICAM-1 expression in human vascular smooth muscle cells. (ahajournals.org)
  • 6 , 7 Transgenic rats with human PRR expression targeted to vascular smooth muscle cells exhibit hypertension and increased plasma aldosterone, suggesting a pathological role of the PRR in raising blood pressure (BP). (ahajournals.org)
  • The clinical relevance of these findings is underscored by the fact that preproendothelin-1 gives rise to endothelin-1, a potent vasoconstrictor and mitogen that regulates vascular tone and remodeling. (ahajournals.org)
  • Cells were cultured in endothelial cell basal medium-2 in the absence and presence of CRP (5 to 20 μg/mL), rosiglitazone (1 μmol/L), and/or vascular endothelial growth factor. (ahajournals.org)
  • Conclusions- Human recombinant CRP, at concentrations known to predict adverse vascular outcomes, directly inhibits EPC differentiation, survival, and function, key components of angiogenesis and the response to chronic ischemia. (ahajournals.org)
  • alpha-1-antitryps
  • Protease inhibitory activity in blood plasma was first reported in the late 1800s, but it was not until the 1950s that the serpins antithrombin and alpha 1-antitrypsin were isolated. (wikipedia.org)
  • Initial research focused on their role in human disease: alpha 1-antitrypsin deficiency is one of the most common genetic disorders, causing emphysema, and antithrombin deficiency results in thrombosis. (wikipedia.org)
  • novel
  • Inhibition of PAI-1 can help to prevent damage to blood vessel walls that occurs as a consequence of chronic high blood pressure, as well as preventing the formation of blood clots that can lead to stroke and heart attack, and potentially also providing a novel treatment mechanism to slow the development of diabetes and obesity. (wikipedia.org)
  • Evaluation of PAI-039 [{1-benzyl-5-[4-(trifluoromethoxy)phenyl]-1H-indol-3-yl}(oxo)acetic acid], a novel plasminogen activator inhibitor-1 inhibitor, in a canine model of coronary artery thrombosis. (wikipedia.org)
  • receptor
  • Thrombin-induced Ca 2+ mobilization and signaling through the insulin receptor and insulin receptor substrate 1 were measured. (haematologica.org)
  • Contact with adipokines for 2 hours disturbed insulin receptor substrate 1 Ser 307 -phosphorylation, while contact for 72 hours caused insulin receptor substrate 1 degradation. (haematologica.org)
  • Platelets from patients with type 2 diabetes showed decreased insulin receptor substrate 1 expression. (haematologica.org)
  • To investigate the role of brain (pro)renin receptor in hypertension, adeno-associated virus-mediated (pro)renin receptor short hairpin RNA was used to knockdown (pro)renin receptor expression in the brain of nontransgenic normotensive and human renin-angiotensinogen double-transgenic hypertensive mice. (ahajournals.org)
  • Real-time PCR and immunostaining were performed to determine (pro)renin receptor, angiotensin II type 1 receptor, and vasopressin mRNA levels. (ahajournals.org)
  • Pro)renin receptor knockdown significantly reduced angiotensin II type 1 receptor and vasopressin levels in double-transgenic mice. (ahajournals.org)
  • In addition, brain-targeted (pro)renin receptor knockdown is associated with downregulation of angiotensin II type 1 receptor and vasopressin levels. (ahajournals.org)
  • We conclude that central (pro)renin receptor contributes to the pathogenesis of hypertension in human renin-angiotensinogen transgenic mice. (ahajournals.org)
  • Brain-targeted PRR knockdown attenuates hypertension and is associated with downregulation of Ang II type 1 (AT 1 ) receptor and arginine vasopressin (AVP) levels. (ahajournals.org)
  • Additional inhibition is mediated by PAI-1 binding to the uPA/uPA receptor complex, resulting in the latter's degradation. (wikipedia.org)
  • extracellular
  • This increase did not result from the release of PAI-1 from intracellular stores, but rather reflected a t-PA-dependent decrease in the PAI-1 content of the Triton X-100 insoluble extracellular matrix (ECM). (rupress.org)
  • 1,2 As a result, levels of extracellular glutamate reach concentrations that induce excessive stimulation of glutamate receptors. (ahajournals.org)
  • Most serpins are protease inhibitors, targeting extracellular, chymotrypsin-like serine proteases. (wikipedia.org)
  • Approximately two-thirds of human serpins perform extracellular roles, inhibiting proteases in the bloodstream in order to modulate their activities. (wikipedia.org)
  • For example, extracellular serpins regulate the proteolytic cascades central to blood clotting (antithrombin), the inflammatory and immune responses (antitrypsin, antichymotrypsin, and C1-inhibitor) and tissue remodelling (PAI-1). (wikipedia.org)
  • Plasminogen activator inhibitor-2 (SerpinB2) has been reported to bind a series of intracellular and extracellular proteins. (wikipedia.org)
  • inhibition
  • In this review, we provide a summary of the preclinical and clinical data that leads to the development of renin inhibitors and offers perspectives on the findings from ALTITUDE, based on new information on RAAS components and their inhibition. (ahajournals.org)
  • Aliskiren demonstrated subnanomolar inhibition of human renin (IC 50 =0.6 nmol/L) with a high degree of distribution in renal glomeruli and small cortical blood vessels. (ahajournals.org)
  • differentiation
  • 1-5 The mobilization and differentiation of bone marrow-derived endothelial progenitor cells (EPCs) has recently been shown to be important in this process of adult neovascularization. (ahajournals.org)
  • tumor
  • We have described a competitive reverse transcription-PCR system for the simultaneous quantification of ER , PR , pS2 , and PAI-1 mRNA in tumor samples. (aacrjournals.org)
  • Here, we evaluated 100 tumor biopsies from breast cancer patients for the mRNA expression of ER , PR , pS2 , and PAI-1 . (aacrjournals.org)
  • pS2 and PAI-1 mRNA expression were not correlated with tumor size, grade, or lymph node involvement. (aacrjournals.org)
  • Plasminogen activator inhibitor type 2 inhibits tumor necrosis factor alpha-induced apoptosis. (wikipedia.org)
  • mRNA
  • However, few data about the mRNA expression of ER , PR , pS2 , and PAI-1 in breast cancer are available, which is mostly due to the limitations of conventional techniques for mRNA analysis. (aacrjournals.org)
  • No correlation between PAI-1 mRNA amount and the expression of the other markers was found. (aacrjournals.org)
  • Molecular
  • 1997). "Human orosomucoid polymorphism: molecular basis of the three common ORM1 alleles, ORM1*F1, ORM1*F2, and ORM1*S". Hum. (wikipedia.org)
  • All these sites are occupied by covalently attached oligosaccharide side-chains in the predominant form of human antithrombin, α-antithrombin, resulting in a molecular weight for this form of antithrombin of 58,200. (wikipedia.org)
  • assays
  • Immunoradiometric assays indicated that t-PA treatment resulted in a fourfold increase in PAI-1 antigen present in the conditioned media. (rupress.org)
  • The assay measures the ability of uPA to activate the plasminogen to plasmin in coupled or indirect assays that contain uPA, plasminogen, and a plasmin-specific synthetic substrate. (abcam.com)
  • mammalian
  • Recombinant antithrombins with properties similar to those of normal human antithrombin have been produced using baculovirus-infected insect cells and mammalian cell lines grown in cell culture. (wikipedia.org)
  • Since apo(a)/Lp(a) derived rather recently in mammalian evolution - only old world monkeys and humans have been shown to harbour Lp(a) - its function might not be vital, but just evolutionarily advantageous under certain environmental conditions, e.g. in case of exposure to certain infectious diseases. (wikipedia.org)
  • 1989
  • 1989). "Regional assignment of the loci for adenylate kinase to 9q32 and for alpha 1-acid glycoprotein to 9q31-q32. (wikipedia.org)
  • phospholipids
  • Lp(a) carries cholesterol and binds atherogenic proinflammatory oxidized phospholipids as a preferential carrier of oxidized phospholipids in human plasma, which attract inflammatory cells to vessel walls and leads to smooth muscle cell proliferation. (wikipedia.org)