Myocardial infarction (MI) is a leading cause of mortality in today's society. Injury to myocardium is a manifestation of the intrinsic cellular response to ischemia and of an extrinsic acute inflammation. Recent pre-clinical studies have revealed that pre-existing natural IgM functions as the critical mediator between the intrinsic and extrinsic responses in injury induction. The goal of this proposal is to expand these novel basic science discoveries at the clinical level. Knowledge gained from this study will provide a new basis for clinical management of myocardial infarction.
The specific aims are as follows:
Aim 1. To determine whether natural IgM antibodies against an ischemia-specific self antigen (non-muscle myosin heavy chain II, NMHC-II) are present in normal individuals and patients with acute myocardial infarction.
Aim 2. To investigate whether the levels of these autoimmune antibodies correlate with the degrees of myocardial injury.

Public Health Relevance

This study will provide important insight of a new mechanism in ischemic myocardial injury, and may identify new markers for myocardial infarction.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HL088527-02
Application #
7846126
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Kirby, Ruth
Project Start
2009-07-01
Project End
2013-06-30
Budget Start
2010-08-17
Budget End
2013-06-30
Support Year
2
Fiscal Year
2010
Total Cost
$203,323
Indirect Cost
Name
Suny Downstate Medical Center
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
040796328
City
Brooklyn
State
NY
Country
United States
Zip Code
11203
Chun, Nicholas; Haddadin, Ala S; Liu, Junying et al. (2017) Activation of complement factor B contributes to murine and human myocardial ischemia/reperfusion injury. PLoS One 12:e0179450
Velickovic, Ivan; Dalloul, Mudar; Wong, Karen A et al. (2015) Complement factor B activation in patients with preeclampsia. J Reprod Immunol 109:94-100
Lee, Haekyung; Ko, Eun Hee; Lai, Mark et al. (2014) Delineating the relationships among the formation of reactive oxygen species, cell membrane instability and innate autoimmunity in intestinal reperfusion injury. Mol Immunol 58:151-9
Charlagorla, Pradeepkumar; Liu, Junying; Patel, Monaliben et al. (2013) Loss of plasma membrane integrity, complement response and formation of reactive oxygen species during early myocardial ischemia/reperfusion. Mol Immunol 56:507-12
Zhang, Ming; Hou, Yunfang Joan; Cavusoglu, Erdal et al. (2013) MASP-2 activation is involved in ischemia-related necrotic myocardial injury in humans. Int J Cardiol 166:499-504
Charchaflieh, Jean; Labaze, Georges I; Li, Pulsar et al. (2012) Overexpression of human SOD1 improves survival of mice susceptible to endotoxic shock. J Inflamm Res 5:51-8
Charchaflieh, Jean; Wei, Jiandong; Labaze, Georges et al. (2012) The role of complement system in septic shock. Clin Dev Immunol 2012:407324
Schwaeble, Wilhelm J; Lynch, Nicholas J; Clark, James E et al. (2011) Targeting of mannan-binding lectin-associated serine protease-2 confers protection from myocardial and gastrointestinal ischemia/reperfusion injury. Proc Natl Acad Sci U S A 108:7523-8
Rahyab, Ali Seyar; Alam, Amit; Kapoor, Aricka et al. (2011) Natural antibody - Biochemistry and functions. Glob J Biochem 2:283-288
Hou, Yunfang Joan; Lee, Daniel C; Ko, Wilson et al. (2010) Perioperative mannan-binding lectin (MBL) patterns in cardiac surgery may correlate with the clinical outcomes in MBL deficient patients. Ann Thorac Surg 90:1357-8

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