Faculty Collaboration Database

Hepatic cell mobilization for protection against ischemic myocardial injury. Sci Rep 2021 Aug 04;11(1):15830

Date

08/06/2021

Pubmed ID

34349157

Pubmed Central ID

PMC8339068

DOI

10.1038/s41598-021-94170-z

Scopus ID

2-s2.0-85111978512 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

The heart is capable of activating protective mechanisms in response to ischemic injury to support myocardial survival and performance. These mechanisms have been recognized primarily in the ischemic heart, involving paracrine signaling processes. Here, we report a distant cardioprotective mechanism involving hepatic cell mobilization to the ischemic myocardium in response to experimental myocardial ischemia-reperfusion (MI-R) injury. A parabiotic mouse model was generated by surgical skin-union of two mice and used to induce bilateral MI-R injury with unilateral hepatectomy, establishing concurrent gain- and loss-of-hepatic cell mobilization conditions. Hepatic cells, identified based on the cell-specific expression of enhanced YFP, were found in the ischemic myocardium of parabiotic mice with intact liver (0.2 ± 0.1%, 1.1 ± 0.3%, 2.7 ± 0.6, and 0.7 ± 0.4% at 1, 3, 5, and 10 days, respectively, in reference to the total cell nuclei), but not significantly in the ischemic myocardium of parabiotic mice with hepatectomy (0 ± 0%, 0.1 ± 0.1%, 0.3 ± 0.2%, and 0.08 ± 0.08% at the same time points). The mobilized hepatic cells were able to express and release trefoil factor 3 (TFF3), a protein mitigating MI-R injury as demonstrated in TFF3^-/- mice (myocardium infarcts 17.6 ± 2.3%, 20.7 ± 2.6%, and 15.3 ± 3.8% at 1, 5, and 10 days, respectively) in reference to wildtype mice (11.7 ± 1.9%, 13.8 ± 2.3%, and 11.0 ± 1.8% at the same time points). These observations suggest that MI-R injury can induce hepatic cell mobilization to support myocardial survival by releasing TFF3.

Author List

Liu SQ, Troy JB, Luan CH, Guillory RJ

Author

Roger J. Guillory II PhD Assistant Professor in the Biomedical Engineering department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cardiotonic Agents
Disease Models, Animal
Liver
Liver Transplantation
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocardial Reperfusion Injury
Trefoil Factor-3