Masashi Sakuma1, Atsushi Tanaka2, Norihiko Kotooka2, Yutaka Hikichi2, Shigeru Toyoda3, Shichiro Abe3, Isao Taguchi4, Koichi Node2, Daniel I Simon5, Teruo Inoue3. 1. Department of Cardiovascular Medicine, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan. Electronic address: masakuma@dokkyomed.ac.jp. 2. Department of Cardiovascular Medicine, Saga University, Faculty of Medicine, Saga, Japan. 3. Department of Cardiovascular Medicine, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan. 4. Department of Cardiology, Koshigaya Hospital, Dokkyo Medical University School of Medicine, Koshigaya, Saitama, Japan. 5. Division of Cardiovascular Medicine, Harrington Heart & Vascular Institute, University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Abstract
BACKGROUND: The alarmin family member myeloid-related protein (MRP)-14 (S100A9), which has been identified by platelet transcriptional profiling as an acute myocardial infarction gene, regulates vascular inflammation and thrombosis. Elevated plasma levels of MRP-8/14 (S100A8/A9) heterodimer predict first and recurrent cardiovascular events. The aim of this study was to elucidate pathophysiological roles of MRP-8/14 in acute coronary syndrome (ACS). METHODS AND RESULTS: In 38 consecutive ACS patients, the MRP-8/14 level in coronary artery blood obtained at thrombus aspiration was higher in 23 patients, in whom aspirated thrombus was confirmed, compared to the 15 patients, in whom it was absent [4.86 (1.95, 8.29) vs 2.94 (1.31, 4.44), P=0.017]. The MRP-8/14 level was correlated with myeloperoxidase (MPO) level (R2=0.52), but not with soluble P-selectin level (R2=0.0002) in the coronary artery blood. Immunohistochemistry of the aspirated thrombus exhibited that expression of MRP8/14 was co-localized with leukocytes positive for activated Mac-1. Finally, in cultured human umbilical vein endothelial cells, MRP-8/14 increased tissue factor expression. CONCLUSIONS: Our findings indicate that MRP-8/14 concentration increases in coronary artery blood in association with thrombus formation in ACS, co-localizes with leukocytes, and is associated with leukocyte activation. MRP-8/14 is positioned as a unique biomarker at the interface of inflammation and thrombosis in ACS.
BACKGROUND: The alarmin family member myeloid-related protein (MRP)-14 (S100A9), which has been identified by platelet transcriptional profiling as an acute myocardial infarction gene, regulates vascular inflammation and thrombosis. Elevated plasma levels of MRP-8/14 (S100A8/A9) heterodimer predict first and recurrent cardiovascular events. The aim of this study was to elucidate pathophysiological roles of MRP-8/14 in acute coronary syndrome (ACS). METHODS AND RESULTS: In 38 consecutive ACS patients, the MRP-8/14 level in coronary artery blood obtained at thrombus aspiration was higher in 23 patients, in whom aspirated thrombus was confirmed, compared to the 15 patients, in whom it was absent [4.86 (1.95, 8.29) vs 2.94 (1.31, 4.44), P=0.017]. The MRP-8/14 level was correlated with myeloperoxidase (MPO) level (R2=0.52), but not with soluble P-selectin level (R2=0.0002) in the coronary artery blood. Immunohistochemistry of the aspirated thrombus exhibited that expression of MRP8/14 was co-localized with leukocytes positive for activated Mac-1. Finally, in cultured human umbilical vein endothelial cells, MRP-8/14 increased tissue factor expression. CONCLUSIONS: Our findings indicate that MRP-8/14 concentration increases in coronary artery blood in association with thrombus formation in ACS, co-localizes with leukocytes, and is associated with leukocyte activation. MRP-8/14 is positioned as a unique biomarker at the interface of inflammation and thrombosis in ACS.
Authors: Gopalkrishna Sreejit; Sunil K Nooti; Andrew J Murphy; Prabhakara R Nagareddy; Robert M Jaggers; Baskaran Athmanathan; Ki Ho Park; Annas Al-Sharea; Jillian Johnson; Albert Dahdah; Man K S Lee; Jianjie Ma Journal: Circulation Date: 2021-11-17 Impact factor: 29.690
Authors: Nathan D Wong; Matthew J Budoff; Keith Ferdinand; Ian M Graham; Erin D Michos; Tina Reddy; Michael D Shapiro; Peter P Toth Journal: Am J Prev Cardiol Date: 2022-03-15