stem-cell-congress-cardiology-2018-posters

Biomedical Research

Volume 29

Page 42

allied

academies

CARDIOLOGY AND CARDIOVASCULAR MEDICINE

STEM CELLS AND REGENERATIVE MEDICINE

International Conference on

J u n e 1 8 - 1 9 , 2 0 1 8 | O s a k a , J a p a n

Joint Event on

MECHANISMS MEDIATING VASCULAR OCCLUSION IN

THROMBOIN FLAMMATORY DISEASES: ROLE OF THIOL

ISOMERASES

Jaehyung Cho

University of Illinois, USA

eal-time intravital microscopic studies have provided compelling evidence that intravascular cell-cell aggregation directly

contributes to vascular occlusion and tissue damage, a leading cause of morbidity andmortality of patients with cardiovascular

diseases. In particular, platelet-leukocyte interactions on the activated endothelium are crucial for the initiation and progression

of thrombotic and inflammatory diseases. Platelet-leukocyte adhesion is mediated mainly through the interactions of platelet

P-selectin and glycoprotein Ibα with neutrophil P-selectin glycoprotein ligand-1 and αMβ2 integrin, respectively. Despite our

knowledge of the major receptors and counter-receptors, it remains poorly understood how the receptor-counter-receptor

interactions are controlled during cardiovascular diseases. Evidence is mounting that the function of plasma proteins and

cell surface receptors involved in thrombosis and inflammation is controlled by oxidation or reduction of allosteric disulfide

bonds. Thiol isomerases catalyze thiol-disulfide exchange and regulate protein folding and function. Intriguingly, despite having

an endoplasmic reticulum retention signal, several thiol isomerases are released from intravascular cells and detected in the

circulation and on the cell surface. We have demonstrated that the plasma level of protein disulfide isomerase (PDI), a prototypic

thiol isomerase, is enhanced during thrombosis and vascular inflammation and that extracellular PDI plays a critical role in platelet-

leukocyte aggregation under thromboinflammatory conditions. In this presentation, I will discuss the molecular mechanism by

which PDI participates in the initiation and progression of thromboinflammatory diseases. A better understanding of themolecular

basis of thiol isomerase-mediated cell-cell interactions will provide insights into the development of novel therapeutic agents for

the prevention and treatment of cardiovascular diseases.

Biomed Res 2018, Volume 29 | DOI: 10.4066/biomedicalresearch-C2-006