Activation of Inflammatory and Pro-Thrombotic Pathways in Acute Stress Cardiomyopathy
AuthorsFitzgibbons, Timothy P.
Edwards, Yvonne J. K.
Bote, Josiah T.
Gerszten, Robert E.
Keaney, John F. Jr.
Zile, Michael R.
Aurigemma, Gerard P.
UMass Chan AffiliationsUMass Metabolic Network
Program in Molecular Medicine
Department of Medicine, Division of Cardiovascular Medicine
Document TypeJournal Article
Keywordsacute myocardial infarction
Cellular and Molecular Physiology
Pathological Conditions, Signs and Symptoms
MetadataShow full item record
AbstractStress cardiomyopathy (SCM) is a unique cardiac disorder that more often occurs in women. SCM presents in a similar fashion as acute myocardial infarction (AMI), with chest pain, ECG changes, and congestive heart failure. The primary distinguishing feature is the absence of thrombotic coronary occlusion in SCM. How this reduction in cardiac function occurs in the absence of coronary occlusion remains unknown. Therefore, we tested the hypothesis that a targeted proteomic comparison of patients with acute SCM and AMI might identify relevant mechanistic differences. Blood was drawn in normal controls (n = 6), women with AMI (n = 12), or women with acute SCM (n = 15). Two-week follow-up samples were available in AMI (n = 4) and SCM patients (n = 11). Relative concentrations of 1,310 serum proteins were measured in each of the 48 samples using the SOMAscan assay. Women with AMI had greater myocyte necrosis, as reflected by a higher peak troponin I concentration (AMI 32.03 +/- 29.46 vs. SCM 2.68 +/- 2.6 ng/ml, p < 0.05). AMI and SCM patients had equivalent reductions in left ventricular ejection fraction [LVEF (%) 39 +/- 12 vs. 37 +/- 12, p = 0.479]. In follow-up, women with SCM had a greater improvement in cardiac function [LVEF (%) 60 +/- 7 vs. 45 +/- 13, p < 0.001]. No differentially expressed proteins were detected (absolute log2-fold change > 1; q < 0.05) between AMI and SCM in the acute or recovery phase. However, when we compared normal controls to patients with AMI, there was differential expression of 35 proteins. When we compared normal controls to patients with SCM, 45 proteins were differentially expressed. In comparison to normal controls, biological processes such as complement, coagulation, and inflammation were activated in both AMI and SCM. There were four proteins that showed a non-significant trend to be increased in acute SCM vs. AMI (netrin-1, follistatin-like 3, kallikrein 7, kynureninase). Despite a lesser degree of myocardial necrosis than AMI, SCM is characterized by a similar activation of inflammatory, complement, and coagulation pathways. These findings may explain reported thromboembolic complications in the short term and elevated risk of mortality in the long term of SCM.
Front Cardiovasc Med. 2017 Aug 3;4:49. doi: 10.3389/fcvm.2017.00049. eCollection 2017. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/40421
RightsCopyright © 2017 Fitzgibbons, Edwards, Shaw, Iskandar, Ahmed, Bote, Shah, Sinha, Gerszten, Keaney, Zile and Aurigemma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Except where otherwise noted, this item's license is described as Copyright © 2017 Fitzgibbons, Edwards, Shaw, Iskandar, Ahmed, Bote, Shah, Sinha, Gerszten, Keaney, Zile and Aurigemma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.