• reductase inhibitors
  • The clinical benefit of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may derive from a qualitative, functional change in atherosclerotic lesions in addition to their lipid-lowering properties. (harvard.edu)
  • 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
  • Arteriosclerosis, Thrombosis, and Vascular Biology 20 (2) (February 1): 556-562. (harvard.edu)
  • 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)
  • 1995
  • Browry VW, Mohr D, Clearly J, Stocker R (1995) Prevention of tocopherol-mediated peroxidation in ubiquinol-20-free human low density lipoprotein. (springer.com)
  • secretion
  • The treatment of isolated human endometriosis epithelial cells with estradiol, medroxyprogesterone acetate, tumor necrosis factor-alpha, and interferon-gamma stimulated measurable eotaxin secretion into the conditioned media. (biomedsearch.com)
  • 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)
  • synthesis
  • Methods- Primary neuronal cultures were pretreated with inhibitors of cholesterol synthesis and cholesterol, and NMDA-induced cell death was determined by measuring release of lactate dehydrogenase. (ahajournals.org)
  • Results- Treatment with the inhibitors of cholesterol synthesis simvastatin, which inhibits the first step of cholesterol synthesis, or AY9944, which inhibits the last step of cholesterol synthesis, protected neurons from NMDA-induced neuronal death by 70% and 54%, respectively. (ahajournals.org)
  • Therefore, statins which block geranylgeraniol synthesis, or geranylgeranyl transferase inhibitors which prevent the attachment of geranylgeraniol to Rho, inhibit Rho membrane translocation and activity. (ahajournals.org)
  • Angiotensin II increases synthesis of plasminogen activator inhibitor-1, so it accelerates the development of atherosclerosis. (wikipedia.org)
  • Just as Dap1 is required for the action of Erg11 in the synthesis of ergosterol in yeast, PGRMC1 regulates the Cyp51-catalyzed demethylation step in human cholesterol synthesis. (wikipedia.org)
  • coagulation
  • 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)
  • 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)
  • 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)
  • 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)
  • mRNA
  • Decreased PAI-1 antigen was correlated with reduced mRNA transcription and activity of the PAI-1 promoter. (harvard.edu)
  • 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)
  • 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)
  • No correlation between PAI-1 mRNA amount and the expression of the other markers was found. (aacrjournals.org)
  • pS2 and PAI-1 mRNA expression were not correlated with tumor size, grade, or lymph node involvement. (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)