Protein compositions changes of circulating microparticles in patients with valvular heart disease and cardiac surgery

Abstract

We previously demonstrated that circulating microparticles from patients with valvular heart disease (VHD) and cardiac surgery with cardiopulmonary bypass(CPB) impaired endothelial function and vasodilation. Protein composition of circulating microparticles is critical in influencing the endothelial function and vasodilation. However, whether the protein compositions of circulating microparticles were changed in patients with VHD and cardiac surgery remains unknown. Circulating microparticles were isolated from age‐matched control subjects (n=50) and patients (n=50) with VHD before and 72 h after cardiac surgery with CPB. Proteomic study was performed by liquid chromatography and mass spectrometry (LC/MS) combined with isobaric tags for relative and absolute quantification (iTRAQ) technique. The different proteins were identified by ProteinPilot™, some of which were considered affecting vascular function and hemodynamic stability were validated by Western blotting. Bio‐informatic analysis of different proteins was also carried out. We found that 849 proteins were identified significantly change in circulating microparticles (p<0.05). Among these, 453 (53.36%) proteins were found in all three groups. 165 (19.43%), 39 (4.59%) and 80 (9.42%) proteins were unique in control group, pre‐operation group and post‐operation group respectively. Compared to control group, there were 181 up‐regulated and 175 down‐regulated proteins in pre‐operation group. Compared to pre‐operation group, there were 89 up‐regulated and 76 down‐regulated proteins in post‐operation group. Bio‐informatic analysis found that these different proteins were different in localization, molecular function and biological process. Western blot confirmed that the pro‐inflammatory proteins in circulating microparticles were significantly increased in VHD patients, which increased even more postoperatively. Pro‐coagulation proteins in circulating microparticles were also dramatically increased in preoperation, but decreased in postoperation. Our data demonstrated that the protein compositions of circulating microparticles were significantly changed in patients with VHD and cardiac surgery. These protein composition changes of circulating microparticles may lead to systemic inflammatory response and disorder of coagulation which may cause difficulties in maintaining the stability of circulation postoperatively.Support or Funding InformationNational Natural Science Foundation of China (Grants 81370370, 81670392, 81600382 and Distinguished Young Scholar Grant 81325001), International cooperation project(2015DFA31070) and National Major Research Program (2016YFC0903000) from the Ministry of Science and Technology of China, Guangdong Natural Science Fund Committee (Grant 2015A030312009), the Changjiang Scholars Program from the Ministry of Education of China, the Guangdong Pearl River Scholars Program, the Sun Yat‐sen University Clinical Research 5010 Program.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.