Regina Le Roux1, Lebogang Mokotedi1, Serena Fourie1, Ashmeetha Manilall1, Sulè Gunter1, Aletta M E Millen2. 1. Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. 2. Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. aletta.millen@wits.ac.za.
Abstract
OBJECTIVES: To determine biologic disease-modifying anti-rheumatic drug effects on inflammation-induced cardiac geometry and function changes. METHODS: Male and female Sprague-Dawley rats (n=92) were divided into four groups: control group, collagen-induced arthritis (CIA) group, anti-TNF-α group and anti-IL-6 group. Inflammation was induced by injecting bovine type-II collagen emulsified in incomplete Freund's adjuvant at the base of the tail, in all groups except the control group. Following the onset of arthritis, the anti-TNF-α group received etanercept, and the anti-IL-6 group received tocilizumab, for six weeks. Left ventricular (LV) geometry and function were assessed with echocardiography and circulating inflammatory markers were measured with ELISA. RESULTS: Relative wall thickness in the CIA and anti-IL-6 groups were increased compared to controls (p<0.001 and p=0.02, respectively). TNF-α inhibition protected against inflammation-induced LV concentric remodelling, as relative wall thickness in the anti-TNF-α group was similar to controls (p=0.55). Systolic function variables were not different between the groups. In all groups inoculated with collagen, myocardial relaxation (lateral e') were impaired compared to controls (all p<0.001). LV filling pressures (E/e') were increased in the CIA, anti-TNF-α and anti-IL-6 groups compared to controls (p<0.001, p<0.001 and p=0.05, respectively). Independent of concentric remodelling, circulating CRP concentrations were associated with decreased e' and increased E/e', while TNF-α concentrations were associated with E/A. CONCLUSIONS: TNF-α inhibition protected against inflammation-induced adverse cardiac remodelling, but not diastolic dysfunction. IL-6 receptors blocker effects on inflammation-induced cardiac changes were inconclusive. Systemic inflammation likely impacts LV concentric remodelling and diastolic dysfunction through distinct pathways.
OBJECTIVES: To determine biologic disease-modifying anti-rheumatic drug effects on inflammation-induced cardiac geometry and function changes. METHODS: Male and female Sprague-Dawley rats (n=92) were divided into four groups: control group, collagen-induced arthritis (CIA) group, anti-TNF-α group and anti-IL-6 group. Inflammation was induced by injecting bovine type-II collagen emulsified in incomplete Freund's adjuvant at the base of the tail, in all groups except the control group. Following the onset of arthritis, the anti-TNF-α group received etanercept, and the anti-IL-6 group received tocilizumab, for six weeks. Left ventricular (LV) geometry and function were assessed with echocardiography and circulating inflammatory markers were measured with ELISA. RESULTS: Relative wall thickness in the CIA and anti-IL-6 groups were increased compared to controls (p<0.001 and p=0.02, respectively). TNF-α inhibition protected against inflammation-induced LV concentric remodelling, as relative wall thickness in the anti-TNF-α group was similar to controls (p=0.55). Systolic function variables were not different between the groups. In all groups inoculated with collagen, myocardial relaxation (lateral e') were impaired compared to controls (all p<0.001). LV filling pressures (E/e') were increased in the CIA, anti-TNF-α and anti-IL-6 groups compared to controls (p<0.001, p<0.001 and p=0.05, respectively). Independent of concentric remodelling, circulating CRP concentrations were associated with decreased e' and increased E/e', while TNF-α concentrations were associated with E/A. CONCLUSIONS: TNF-α inhibition protected against inflammation-induced adverse cardiac remodelling, but not diastolic dysfunction. IL-6 receptors blocker effects on inflammation-induced cardiac changes were inconclusive. Systemic inflammation likely impacts LV concentric remodelling and diastolic dysfunction through distinct pathways.
Authors: Theis Christian Tønnessen; Arne Olav Melleby; Ida Marie Hauge-Iversen; Emil Knut Stenersen Espe; Mohammed Shakil Ahmed; Thor Ueland; Espen Andre Haavardsholm; Sara Marie Atkinson; Espen Melum; Håvard Attramadal; Ivar Sjaastad; Leif Erik Vinge Journal: PLoS One Date: 2022-01-25 Impact factor: 3.240
Authors: Ashmeetha Manilall; Lebogang Mokotedi; Sulè Gunter; Regina Le Roux; Serena Fourie; Colleen A Flanagan; Aletta M E Millen Journal: Physiol Rep Date: 2021-11
Authors: Sulè Gunter; Frederic S Michel; Serena S Fourie; Mikayra Singh; Regina le Roux; Ashmeetha Manilall; Lebogang P Mokotedi; Aletta M E Millen Journal: PLoS One Date: 2022-02-25 Impact factor: 3.240