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MG53 suppresses NF-κB activation to mitigate age-related heart failure
Xiaoliang Wang, … , Chuanxi Cai, Jianjie Ma
Xiaoliang Wang, … , Chuanxi Cai, Jianjie Ma
Published July 22, 2021
Citation Information: JCI Insight. 2021;6(17):e148375. https://doi.org/10.1172/jci.insight.148375.
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Research Article Aging Cardiology

MG53 suppresses NF-κB activation to mitigate age-related heart failure

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Abstract

Aging is associated with chronic oxidative stress and inflammation that affect tissue repair and regeneration capacity. MG53 is a TRIM family protein that facilitates repair of cell membrane injury in a redox-dependent manner. Here, we demonstrate that the expression of MG53 was reduced in failing human hearts and aged mouse hearts, concomitant with elevated NF-κB activation. We evaluated the safety and efficacy of longitudinal, systemic administration of recombinant human MG53 (rhMG53) protein in aged mice. Echocardiography and pressure-volume loop measurements revealed beneficial effects of rhMG53 treatment in improving heart function of aged mice. Biochemical and histological studies demonstrated that the cardioprotective effects of rhMG53 are linked to suppression of NF-κB–mediated inflammation, reducing apoptotic cell death and oxidative stress in the aged heart. Repetitive administration of rhMG53 in aged mice did not have adverse effects on major vital organ functions. These findings support the therapeutic value of rhMG53 in treating age-related decline in cardiac function.

Authors

Xiaoliang Wang, Xiuchun Li, Hannah Ong, Tao Tan, Ki Ho Park, Zehua Bian, Xunchang Zou, Erin Haggard, Paul M. Janssen, Robert E. Merritt, Timothy M. Pawlik, Bryan A. Whitson, Nahush A. Mokadam, Lei Cao, Hua Zhu, Chuanxi Cai, Jianjie Ma

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Figure 2

Systemic administration of rhMG53 mitigates HF in aged mice.

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Systemic administration of rhMG53 mitigates HF in aged mice.
(A) Schemat...
(A) Schematic protocol for the 6-week daily administration of rhMG53 in aged mice. (B) Survival curve for mice with systemic administration of rhMG53 (n = 30) or saline control (n = 30); 15 males and 15 females mice per group. (C) Longitudinal echocardiography measurements of aged mice with saline and rhMG53 treatments. (D) Representative pressure-volume loop for the assessment of aged mouse heart function after treatment with saline or rhMG53. (E) Quantitative analysis of the left ventricular EF for the PV-loop measurements for mice treated with saline and rhMG53. Open symbols, male mice; closed symbols, female mice. Data are expressed as mean ± SEM. Differences were analyzed for significance by unpaired t test (C and E); P values are presented in the individual panels.

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