| Title: |
Exogenous Ubiquitin Reduces Inflammatory Response and Preserves Myocardial Function 3 Days Post-Ischemia-Reperfusion Injury |
| Authors: |
Scofield, Stephanie L. C.; Dalal, Suman; Lim, Kristina A.; Thrasher, Patsy R.; Daniels, Christopher R.; Peterson, Jonathan M.; Singh, Mahipal |
| Source: |
ETSU Faculty Works |
| Publisher Information: |
Digital Commons @ East Tennessee State University |
| Publication Year: |
2019 |
| Collection: |
Digital Commons @ East Tennessee State University |
| Subject Terms: |
heart; inflammation; ischemia-reperfusion; macrophages; neutrophils; ubiquitin; Biomedical Sciences; Health Sciences; Medical Physiology |
| Description: |
β-Adrenergic receptor (β-AR) stimulation increases extracellular levels of ubiquitin (UB) in myocytes, and exogenous UB decreases β-AR-stimulated myocyte apoptosis and myocardial fibrosis. Here, we hypothesized that exogenous UB modulates the inflammatory response, thereby playing a protective role in cardiac remodeling after ischemia-reperfusion (I/R) injury. C57BL/6 mice infused with vehicle or UB (1 μg·g−1·h−1) were subjected to myocardial I/R injury. Functional and biochemical parameters of the heart were examined 3 days post-I/R. Heart weight-to-body weight ratios were similarly increased in I/R and UB + I/R groups. The area at risk and infarct size were significantly lower in UB + I/R versus I/R groups. Measurement of heart function using echocardiography revealed that I/R decreases percent fractional shortening and percent ejection fraction. However, the decrease in fractional shortening and ejection fraction was significantly lower in the UB + I/R group. The UB + I/R group displayed a significant decrease in inflammatory infiltrates, neutrophils, and macrophages versus the I/R group. Neutrophil activity was significantly lower in the UB + I/R group. Analysis of the concentration of a panel of 23 cytokines/chemokines in the serum using a Bio-Plex assay revealed a significantly lower concentration of IL-12 subunit p40 in the UB + I/R versus I/R group. The concentration of monocyte chemotactic protein-1 was lower, whereas the concentration of macrophage inflammatory protein-1α was significantly higher, in the UB+I/R group versus the sham group. Expression of matrix metalloproteinase (MMP)-2 and activity of MMP-9 were higher in the UB + I/R group versus the I/R group. Levels of ubiquitinated proteins and tissue inhibitor of metalloproteinase 2 expression were increased to a similar extent in both I/R groups. Thus, exogenous UB plays a protective role in myocardial remodeling post-I/R with effects on cardiac function, area at risk/infarct size, the inflammatory response, levels of serum cytokines/chemokines, ... |
| Document Type: |
text |
| Language: |
unknown |
| Relation: |
https://doi.org/10.1152/ajpheart.00654.2018 |
| DOI: |
10.1152/ajpheart.00654.2018 |
| Availability: |
https://dc.etsu.edu/etsu-works/5572; https://doi.org/10.1152/ajpheart.00654.2018 |
| Accession Number: |
edsbas.FE5B2FE8 |
| Database: |
BASE |