More and more evidence indicates that microvesicles (MVs) play a key role in cell-to-cell communication. The MVs are circular fragments of membrane released from the endosomal compartment as exosomes or shed from the cell surface membranes of most types. Components of donor cells are incorporated into MVs that contain bioactive lipids, proteins, genetic cargoes. MVs derived from stem cells may reprogram cells that survived in injury tissue and favor tissue regeneration by delivering their bioactive cargoes to influence the behaviors of recipient cells. Compared with mesenchymal stem cells (MSCs), MVs derived from MSCs were found to mimic the beneficial effects of these cells. These proregenerative effects mediated by MVs can be explained by the fact that MVs are enriched in bioactive lipids, anti-apoptotic and pro-stimulatory growth factors or cytokines, and deliver mRNAs, regulatory miRNAs and proteins that improve overall cell function. Therefore, it opens novel perspectives in exploiting these MVs in tissue regeneration and repair. In addition, the use of MVs instead of stem cells could represent a safe and potentially more advantageous alternative to cell-therapy approaches.
ObjectivesTo investigate the correlation of warfarin dose genetic and polymorphism of Han-patients after heart valve replacement, to forecast the anticoagulation therapy with warfarin reasonable dosage, and to realize individualized management of anticoagulation monitoring. MethodsWe selected 103 patients between January 1, 2011 and December 31, 2012 in West China Hospital of Sichuan University who were treated by oral warfarin after heart valve replacement with monitoring anticoagulation by international normalized ratio (INR) in Anticoagulation Therapy Database of Chinese Patients after Heart Valve Replacement. There were 32 males and 71 female at age of 21-85 (48.64± 11.66) years. All the patients' CYP2C9 and VKORC1 genetic polymorphisms were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP) method and gene sequencing technology. Warfarin concentration in plasma was determined by high performance liquid chromatography (HPLC) method. The activity of coagulation factorⅡ, Ⅶ, Ⅸ, Ⅹwas determined by Sysmex CA7000 analyzer. ResultsThe multivariate linear regression analysis showed that age, body surface area, and coagulation factor activity had no significant effect on warfarin dosage. While the gene polymor-phisms of CYP2C9 and VKORC1, warfarin concentration, and age had significant contributions to the overall variability in warfarin dose with decisive coefficients at 1.2%, 26.5%, 43.4%, and 5.0% respectively. The final equation was:Y=1.963-0.986× (CYP2C9* 3) +0.893× (VKORC1-1639) +0.002× (warfarin concentration)-0.019× (age). ConclusionMultiple regression equation including gene polymorphisms of CYP2C9 and VKORC1, non-genetic factors of coagulation factor activity, warfarin concentration, age, and body surface area can predict reasonable dosage of warfarin for anticoagulation to achieve individualized management of anticoagulation monitoring and reduce the anticoagulation complications.