title: Splenic release of platelets contributes to increased circulating platelet size and inflammation after myocardial infarction.
abstract: Acute myocardial infarction (AMI) is characterized by a rapid increase in circulating platelet size but the mechanism for this is unclear. Large platelets are hyperactive and associated with adverse clinical outcomes. We determined mean platelet volume (MPV) and platelet-monocyte conjugation (PMC) using blood samples from patients, and blood and the spleen from mice with AMI. We further measured changes in platelet size, PMC, cardiac and splenic contents of platelets and leucocyte infiltration into the mouse heart. In AMI patients, circulating MPV and PMC increased at 1-3 h post-MI and MPV returned to reference levels within 24 h after admission. In mice with MI, increases in platelet size and PMC became evident within 12 h and were sustained up to 72 h. Splenic platelets are bigger than circulating platelets in normal or infarct mice. At 24 h post-MI, splenic platelet storage was halved whereas cardiac platelets increased by 4-fold. Splenectomy attenuated all changes observed in the blood, reduced leucocyte and platelet accumulation in the infarct myocardium, limited infarct size and alleviated cardiac dilatation and dysfunction. AMI-induced elevated circulating levels of adenosine diphosphate and catecholamines in both human and the mouse, which may trigger splenic platelet release. Pharmacological inhibition of angiotensin-converting enzyme, β1-adrenergic receptor or platelet P2Y12 receptor reduced platelet abundance in the murine infarct myocardium albeit having diverse effects on platelet size and PMC. In conclusion, AMI evokes release of splenic platelets, which contributes to the increase in platelet size and PMC and facilitates myocardial accumulation of platelets and leucocytes, thereby promoting post-infarct inflammation.
authors.affiliation: Experimental Cardiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Gao
authors.affiliation: Experimental Cardiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia Alfred Heart Centre, Alfred Hospital, Melbourne, VIC 3004, Australia.
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Moore
authors.affiliation: Experimental Cardiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Third Hospital of Peking University, Beijing 100191, China.
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Experimental Cardiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Han
authors.affiliation: Experimental Cardiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
authors.forename: Yidan
authors.initials: Y
authors.lastname: Su
authors.affiliation: Experimental Cardiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Tsai
authors.affiliation: Experimental Cardiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Experimental Cardiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Experimental Cardiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.
authors.forename: Gavin W
authors.initials: GW
authors.lastname: Lambert
authors.affiliation: Experimental Cardiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
authors.forename: Helen
authors.initials: H
authors.lastname: Kiriazis
authors.affiliation: Department of Cardiology, Third Hospital of Peking University, Beijing 100191, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Experimental Cardiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia Central Clinical School, Monash University, Melbourne, VIC 3004, Australia Alfred Heart Centre, Alfred Hospital, Melbourne, VIC 3004, Australia.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Dart
authors.affiliation: Experimental Cardiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia Central Clinical School, Monash University, Melbourne, VIC 3004, Australia xiao-jun.du@bakeridi.edu.au.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Du
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D048429:Cell Size; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology*; D009203:Myocardial Infarction / Q000097:blood* / Q000503:physiopathology; D009206:Myocardium / Q000166:cytology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010976:Platelet Count
chemical_list: D007703:Peptidyl-Dipeptidase A
keywords: catecholamines; infarct size; inflammation; mean platelet volume; monocytes; myocardial infarction; platelets; spleen