Comparison of the effects of CORM-2, CORM-3 and CORM-A1 on coagulation in human plasma

Abstract

Carbon monoxide derived from the catalytic action of heme oxygenase-1 or carbon monoxide-releasing molecules (CORMs) has been found to potentially be an anticoagulant or procoagulant agent. Of interest, two water-soluble CORMs, CORM-3 and CORM-A1, recently became commercially available. Thus, the purpose of the present study was to assess and compare the effects of the previously well studied CORM-2 to the effects of CORM-3 and CORM-A1 on coagulation in citrated human plasma with thrombelastography. Plasma exposed to CORMs was incubated at 37°C for at least one carbon monoxide release half-time, and then tissue factor-activated coagulation was commenced with calcium addition. CORM-2 and CORM-3 enhanced the velocity of clot formation and thrombus strength in a similar manner, whereas CORM-A1 did not affect coagulation. However, CORM-A1 did diminish tissue-type plasminogen activator initiated fibrinolysis. The similarity in effect on coagulation by CORM-2 and CORM-3 was likely secondary to the relatively inert effect of their ruthenium-containing carrier molecule, whereas the boron-containing CORM-A1 may have had no effect secondary to boron binding to fibrinogen, preventing carbon monoxide-mediated changes in fibrinogen protein structure via attached heme group(s). Future investigations with CORMs should have special attention to confounding effects of the carrier molecule.

Effects of Heme Modulation on Ovophis and Trimeresurus Venom Activity in Human Plasma

“…As for exposure to CORM-2 to characterize the effects of CO on venom activity, the subsequent four experimental conditions were utilized: (1) control—no venom, DMSO 1% addition ( v / v ) in PBS; (2) venom condition—venom, DMSO 1% addition ( v / v ) in PBS; (3) CO-exposed—venom, CORM-2 1% addition in DMSO (100 µM final concentration; and (4) iRM-exposed—venom, inactivated CORM-2 1% addition in DMSO (100 µM final concentration). CORM-2 was inactivated as published elsewhere [ 19 ]. If venom was found to not be inhibited by 100 µM CORM-2, a concentration of 1000 µM CORM-2 and iRM was used instead, as this is the greatest concentration utilized to inhibit venom activity prior to in vivo administration [ 20 ].…”

Direct Inhibitory Effects of Carbon Monoxide on Six Venoms Containing Fibrinogenolytic Metalloproteinases

“…Exposure of the venoms in isolation to CO was accomplished by adding CORM-2 to subsequently described solutions of venom in PBS. To isolate the effects of CO from the carrier molecule of CORM-2, a 100-lM solution of CORM-2 was placed in a sealed plastic tube and incubated in a to a 37°C water bath for 18 hr in order to release CO and become inactive (iCORM-2) as has been previously described [18]. To test the effects of CO on venom activity, a 1-ml quantity of venom in PBS was prepared for each condition subsequently presented.…”

Serial Analysis of 38 Proteins during the Progression of Human Breast Tumor in Mice Using an Antibody Colocalization Microarray*

“…For the diagnosis and monitoring of recurrence, the differential change in concentration (sometimes also called the velocity ( 1 )) is often more accurate. Indeed, this measure intrinsically takes into account personal variation and defines individual baselines.…”

“…Proteins in blood have long been used as biomarkers for cancer disease management ( 1 , 2 ). Proteins up-regulated in cancer cells may be found at higher concentration in blood, and their use for disease prognosis and response to therapy is well established ( 3 ).…”