Dataset Information

Inflammation-induced left ventricular fibrosis is partially mediated by tumor necrosis factor-α.

ABSTRACT:

Objective

To determine the mechanisms of inflammation-induced left ventricular (LV) remodeling and effects of blocking circulating tumor necrosis factor alpha (TNF-α) in a model of systemic inflammation.

Methods

Seventy Sprague-Dawley rats were divided into three groups: the control group, the collagen-induced arthritis (CIA) group, and the anti-TNF-α group. Inflammation was induced in the CIA and anti-TNF-α groups. Following the onset of arthritis, the anti-TNF-α group received the TNF-α inhibitor, etanercept, for 6 weeks. LV geometry and function were assessed with echocardiography. Circulating inflammatory markers were measured by ELISA and LV gene expression was assessed by comparative TaqMan® polymerase chain reaction.

Results

The LV relative gene expression of pro-fibrotic genes, transforming growth factor β (TGFβ) (p = 0.03), collagen I (Col1) (p < 0.0001), and lysyl oxidase (LOX) (p = 0.002), was increased in the CIA group compared with controls, consistent with increased relative wall thickness (p = 0.0009). Col1 and LOX expression in the anti-TNF-α group were similar to controls (both, p > 0.05) and tended to be lower compared to the CIA group (p = 0.06 and p = 0.08, respectively), and may, in part, contribute to the decreased relative wall thickness in the anti-TNF-α group compared to the CIA group (p = 0.03). In the CIA group, the relative gene expression of matrix metalloproteinase 2 (MMP2) and MMP9 was increased compared to control (p = 0.04) and anti-TNF-α (p < 0.0001) groups, respectively.

Conclusion

Chronic systemic inflammation induces fibrosis and dysregulated LV extracellular matrix remodeling by increasing local cardiac pro-fibrotic gene expression, which is partially mediated by TNF-α. Inflammation-induced LV diastolic dysfunction is likely independent of myocardial fibrosis.

SUBMITTER: Manilall A

PROVIDER: S-EPMC8554769 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Inflammation-induced left ventricular fibrosis is partially mediated by tumor necrosis factor-α.

Manilall Ashmeetha A Mokotedi Lebogang L Gunter Sulè S Le Roux Regina R Fourie Serena S Flanagan Colleen A CA Millen Aletta M E AME

Physiological reports 20211101 21

<h4>Objective</h4>To determine the mechanisms of inflammation-induced left ventricular (LV) remodeling and effects of blocking circulating tumor necrosis factor alpha (TNF-α) in a model of systemic inflammation.<h4>Methods</h4>Seventy Sprague-Dawley rats were divided into three groups: the control group, the collagen-induced arthritis (CIA) group, and the anti-TNF-α group. Inflammation was induced in the CIA and anti-TNF-α groups. Following the onset of arthritis, the anti-TNF-α group received t ...[more]

PMID: 34713972

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Dataset Information

Inflammation-induced left ventricular fibrosis is partially mediated by tumor necrosis factor-α.

Objective

Methods

Results

Conclusion

Publications

Inflammation-induced left ventricular fibrosis is partially mediated by tumor necrosis factor-α.

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