OC 34.5 - Fibrin and von Willebrand factor deposition, and neutrophil extracellular traps formation during human coronary atherogenesis

Monday, June 24, 2024

10:30 – 10:45 ICT

Room: Ballroom B4

Presenting Author(s)

Eriko Nakamura, MD, PhD

Clinical fellow
Department of Pathology, Faculty of Medicine, University of Miyazaki
Miyazaki, Miyazaki, Japan

Co-Author(s)

SH

Saki Horiuchi

Medical student
Department of Pathology, Faculty of Medicine, University of Miyazaki
Miyazaki, Miyazaki, Japan
KM

Kazunari Maekawa

assistant professor
Department of Pathology, Faculty of Medicine, University of Miyazaki
Miyazaki, Miyazaki, Japan
Nobuyuki Oguri

medical stuff,　graduate student
Department of Pathology, Faculty of Medicine, University of Miyazaki
Miyazaki, Miyazaki, Japan
Toshihiro Gi

assistant professor
Department of Pathology, Faculty of Medicine, University of Miyazaki
Miyazaki, Miyazaki, Japan
SM

Sayaka Moriguchi Goto

assistant professor
Department of Pathology, Faculty of Medicine, University of Miyazaki
Miyazaki, Miyazaki, Japan
Murasaki Aman, MD, PhD

Assistant professor
Department of Pathology, Faculty of Medicine, University of Miyazaki
Miyazaki, Miyazaki, Japan
YA

Yujiro Asada

Doctor
Department of Pathology,Miyazaki medical association hospital
Miyazaki, Miyazaki, Japan
Atsushi Yamashita

professor
Department of Pathology, Faculty of Medicine, University of Miyazaki
Miyazaki, Miyazaki, Japan

Background: Fibrin, von Willebrand factor (VWF), and neutrophil extracellular traps (NETs) are present in acute coronary thrombotic plaques. However, the presence and extent of fibrin, VWF, and NETs in early to unstable coronary atherosclerotic lesions remain unclear.

Aims: To reveal the presence and extent of fibrin, VWF, and NETs formation in early to unstable human coronary atherosclerotic lesions.

Methods: Coronary sections from autopsy patients with non-cardiac death (n=5, 37 sections) and ischemic heart diseases (n= 12, 55 sections) were classified according to an established atherosclerosis classification; diffuse intimal thickening, pathological intimal thickening, fibrous cap atheroma, fibrocalcified plaque, thin-cap fibroatheroma, and ruptured plaque, and were evaluated presence or absence of intraplaque hemorrhage. We immunohistochemically assessed with anti-fibrin, VWF, CD66b (a marker of neutrophil), and citrullinated histone H3 (Cit-H3, a marker of NETs) antibodies.

Results: Fibrin depositions were observed in pathological intimal thickening, necrotic core of atheromas, and were abundant in thin-cap fibroatheroma and ruptured plaque. VWF depositions were observed in necrotic core of atheromas, and were abundant in ruptured plaque. CD66b and Cit-H3 expressions were rarely observed except in the necrotic core of thin-cap fibroatheroma and ruptured plaque, and were abundant in ruptured plaque (Figure). In non-ruptured plaques, fibrin deposition and Cit-H3 expression were higher in hemorrhagic plaques than those in non-hemorrhagic plaques.

Conclusion(s): These results suggest that fibrin deposition occurs in pathological intimal thickening and necrotic cores without rupture in human coronary artery. Intraplaque hemorrhage may promote fibrin and NETs formation in non-ruptured atheromas. Abundance of neutrophilic infiltrate, NETs formation and VWF deposition may be a response to plaque rupture.