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Trans-system mechanisms against ischemic myocardial injury.

Shu Q. Liu1, Xin-Liang Ma2, Gangjian Qin3, Qingping Liu4, Yan-Chun Li5,

Yu H. Wu1.

Compr Physiol. 2015 ;5(1):167-92.1.Biomedical Engineering Department, Northwestern University, Evanston, Illinois.

2. Department of Emergency Medicine, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania.

3.Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

4. Carbohydrate and Lipid Metabolism Research Laboratory, College of Life Science and Technology, Dalian University, Dalian, China

5. Department of Medicine, Division of Biological Sciences, The University of Chicago, Chicago, Illinois.


A mammalian organism possesses a hierarchy of naturally evolved protective mechanisms against ischemic myocardial injury at the molecular, cellular, and organ levels. These mechanisms comprise regional protective processes, including upregulation and secretion of paracrine cell-survival factors, inflammation, angiogenesis, fibrosis, and resident stem cell-based cardiomyocyte regeneration. There are also interactive protective processes between the injured heart, circulation, and selected remote organs, defined as trans-system protective mechanisms, including upregulation and secretion of endocrine cell-survival factors from the liver and adipose tissue as well as mobilization of bone marrow, splenic, and hepatic cells to the injury site to mediate myocardial protection and repair. The injured heart and activated remote organs exploit molecular and cellular processes, including signal transduction, gene expression, cell proliferation, differentiation, migration, mobilization, and/or extracellular matrix production, to establish protective mechanisms. Both regional and trans-system cardioprotective  mechanisms are mediated by paracrine and endocrine messengers and act in coordination and synergy to maximize the protective effect, minimize  myocardial  infarction, and improve myocardial function, ensuring the survival and timely repair of the injured heart. The concept of the trans-system protective mechanisms may be generalized to other organ systems-injury in one organ may initiate regional as well as trans-system protective responses, thereby minimizing injuryand ensuring the survival of the entire organism. Selected trans-system processes may serve as core protective  mechanisms that can be exploited by selected organs in injury. These naturally evolved protective mechanisms are the foundation for developing protective strategies for myocardial infarction and injury-induced disorders in other organ systems.

© 2015 American Physiological Society.

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Additional Information

 Boosting myocardial tolerance to ischemia by exploiting trans-system protective mechanisms. Myocardial ischemia activates not only regional, but also trans-system protective mechanisms involving the circulation and remote non-injured organs. Regional protective mechanisms include upregulation and secretion of paracrine cell-survival factors such as adenosine, bradykinin, and opioids from the injured myocardium. Trans-system protective mechanisms involve the liver and other organs, which upregulate and release endocrine protective factors, such as fibroblast growth factor 21 and trefoil factor 3. Both regional and trans-system protective factors act in coordination and synergy to maximize the protective impact. Messengers from the injured myocardium are required to activate the trans-system mechanisms. Other injured organs may also exploit the trans-system mechanisms for protection, although the messengers and protective factors may vary. These naturally evolved protective mechanisms are the foundation for developing therapeutic strategies for myocardial infarction and other forms of injury.

Trans-System Mechanisms Against Ischemic Myocardial Injury