Comprehensive Proteome Profiling of Platelet Identified a Protein Profile Predictive of Responses to An Antiplatelet Agent Sarpogrelate.
Sarpogrelate is an antiplatelet agent widely used to treat arterial occlusive diseases. Evaluation of platelet aggregation is essential to monitor therapeutic effects of sarpogrelate. Currently, no molecular signatures are available to evaluate platelet aggregation. Here, we performed comprehensive proteome profiling of platelets collected from 18 subjects before and after sarpogrelate administration using LC-MS/MS analysis coupled with extensive fractionation. Of 5423 proteins detected, we identified 499 proteins affected by sarpogrelate and found that they strongly represented cellular processes related to platelet activation and aggregation, including cell activation, coagulation, and vesicle-mediated transports. Based on the network model of the proteins involved in these processes, we selected three proteins (cut-like homeobox 1; coagulation factor XIII, B polypeptide; and peptidylprolyl isomerase D) that reflect the platelet aggregation-related processes after confirming their alterations by sarpogrelate in independent samples using Western blotting. Our proteomic approach provided a protein profile predictive of therapeutic effects of sarpogrelate.
From the ‡Department of Chemistry, Research Institute for Natural Sciences, Korea University, Seoul, 02841, Republic of Korea.
Hangyeore
H
Lee
§Department of New Biology and Center for Plant Aging Research, Institute for Basic Science, Daegu Gyeongbuk Institute of Science and Technology, Daegu, 42988, Republic of Korea.
Sehyun
S
Chae
¶Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Republic of Korea.|‖Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, 06351, Republic of Korea.
Jisook
J
Park
From the ‡Department of Chemistry, Research Institute for Natural Sciences, Korea University, Seoul, 02841, Republic of Korea.
Jingi
J
Bae
‖Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, 06351, Republic of Korea.
Eun-Bi
EB
Go
From the ‡Department of Chemistry, Research Institute for Natural Sciences, Korea University, Seoul, 02841, Republic of Korea.
Su-Jin
SJ
Kim
From the ‡Department of Chemistry, Research Institute for Natural Sciences, Korea University, Seoul, 02841, Republic of Korea.
Hokeun
H
Kim
§Department of New Biology and Center for Plant Aging Research, Institute for Basic Science, Daegu Gyeongbuk Institute of Science and Technology, Daegu, 42988, Republic of Korea; dhhwang@postech.ac.kr sw_lee@korea.ac.kr suddenbz@skku.edu.
Daehee
D
Hwang
From the ‡Department of Chemistry, Research Institute for Natural Sciences, Korea University, Seoul, 02841, Republic of Korea; dhhwang@postech.ac.kr sw_lee@korea.ac.kr suddenbz@skku.edu.
Sang-Won
SW
Lee
¶Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Republic of Korea; dhhwang@postech.ac.kr sw_lee@korea.ac.kr suddenbz@skku.edu.
Soo-Youn
SY
Lee
D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002853:Chromatography, Liquid; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects*; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D040901:Proteomics / Q000379:methods*; D013386:Succinates / Q000008:administration & dosage*; D053719:Tandem Mass Spectrometry
D010975:Platelet Aggregation Inhibitors; D013386:Succinates; C064294:sarpogrelate