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Review
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Use of Multifactorial Treatments to Address the Challenge of Translating Experimental Myocardial Infarct Reduction Strategies

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Review

Use of Multifactorial Treatments to Address the Challenge of Translating Experimental Myocardial Infarct Reduction Strategies

Julie L Horton et al. Int J Mol Sci.

Abstract

Myocardial tissue damage that occurs during an ischemic event leads to a spiraling deterioration of cardiac muscle structural and functional integrity. Reperfusion is the only known efficacious strategy and is the most commonly used treatment to reduce injury and prevent remodeling. However, timing is critical, and the procedure is not always feasible for a variety of reasons. The complex molecular basis for cardioprotection has been studied for decades but formulation of a viable therapeutic that can significantly attenuate myocardial injury remains elusive. In this review, we address barriers to the development of a fruitful approach that will substantially improve the prognosis of those suffering from this widespread and largely unmitigated disease. Furthermore, we proffer that ephrinA1, a candidate molecule that satisfies many of the important criteria discussed, possesses robust potential to overcome these hurdles and thus offers protection that surpasses the limitations currently observed.

Keywords: cardioprotection; ephrinA1; ischemia; myocardial infarction; reperfusion; therapeutic strategies.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Literature search on Pubmed for the terms related to cardiac ischemia tissue injury show 16,752 publications since 1978. Search details: (“heart”[MeSH Terms] OR “heart”[All Fields] OR “cardiac”[All Fields]) OR (“ischaemia”[All Fields] OR “ischemia”[MeSH Terms] OR “ischemia”[All Fields]) OR (“tissues”[MeSH Terms] OR “tissues”[All Fields] OR “tissue”[All Fields]) OR (“wounds and injuries”[MeSH Terms] OR (“wounds”[All Fields] AND “injuries”[All Fields]) OR “wounds and injuries”[All Fields] OR “injury”[All Fields]) AND (“1978/01/01”[PDAT]: “2018/11/29”[PDAT]): https://www.ncbi.nlm.nih.gov/pubmed/; site visited on 29 November 2018.
Figure 2
Figure 2
Potential Mechanisms of EA1-Fc Mediated Cardioprotection. Treatment with Ephrin A1-Fc (EA1-Fc) in a mouse model of myocardial infarction (MI) was shown to alter expression of five Ephrin receptors (EphA1-A4 and EphA6) as well as endogenous EA1 ligand when compared to the vehicle treated MI group. Canonical ephrin signaling regulates a wide-variety of physiological processes. The cardioprotective role of EA1-Fc may be attributed to ephrin signaling. In support of this, in the EA1-Fc MI group, indicators of decreased apoptosis, increased autophagy, and decreased inflammation were observed. The possibility also exists that EA1-Fc injection is cardioprotective through a mechanism that is not normally attributed to ephrin signaling.
Figure 3
Figure 3
Comparison of pharmacological cardioprotective strategies’ efficacy to reduce infarct size due to ischemia/reperfusion injury [106].

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