Interaction of genetic background and exercise training intensity on endothelial function in mouse aorta

Abstract

The purpose of this study was to characterize the genetic contribution to endothelial adaptation to exercise training. Vasoreactivity was assessed in aortas from four inbred mouse strains (129S1, B6, NON, and SJL) after 4 weeks of moderate intensity continuous exercise training (MOD), high intensity interval training (HIT) or in sedentary controls (SED). Intrinsic variations in endothelium-dependent vasorelaxation (EDR) to acetylcholine (ACh) as well as vasocontractile responses were observed across SED groups. For responses to exercise training, there was a significant interaction between mouse strain and training intensity on EDR. Exercise training had no effect on EDR in aortas from 129S1 and B6 mice. In NON, EDR was improved in aortas from MOD and HIT compared with respective SED, accompanied by diminished responses to PE in those groups. Interestingly, EDR was impaired in aorta from SJL HIT compared with SED. The transcriptional activation of endothelial genes was also influenced by the interaction between mouse strain and training intensity. The number of genes altered by HIT was greater than MOD, and there was little overlap between genes altered by HIT and MOD. HIT was associated with gene pathways for inflammatory responses. NON MOD genes showed enrichment for vessel growth pathways. These findings indicate that exercise training has non-uniform effects on endothelial function and transcriptional activation of endothelial genes depending on the interaction between genetic background and training intensity.

Systematic Review and Meta-Analysis of Endurance Exercise Training Protocols for Mice

“…However, the precision and dispersion of the effect estimates are similar for both C57BL/6 and "Other" subgroups suggesting that the variability in response to training is comparable. Thus, the strain-dependent differences in changes in exercise capacity with exercise training reported by Massett and colleagues (Massett and Berk, 2005;Avila et al, 2017;Kim et al, 2020) might be specific to the exercise training and testing paradigm used in those studies. Each of those studies utilized similar exercise training parameters with some strain-specific adjustments which facilitated direct comparisons with minimal variation between training protocols.…”

“…This result implies that C57BL/6 mice show greater biochemical adaptations to exercise training than mice from other strains. This contrasts with performance-based outcomes where C57BL/6 mice have low to moderate responses to training compared with other strains (Massett and Berk, 2005;Avila et al, 2017;Kim et al, 2020). Future research investigating the effect of mouse strain on exercise training responses should consider including multiple strains within the same study design and measuring both performance-based and biochemical markers of training efficacy.…”

“…For subgroup analyses, strains were coded as C57BL/6 or “Other.” The “Other” group included data from 27 strains. As with sex comparisons, only three articles included data from multiple mouse strains ( Massett and Berk, 2005 ; Avila et al, 2017 ; Kim et al, 2020 ). Each of those publications reported significant strain-dependent changes in exercise capacity in response to exercise training.…”

“…The effect size for ILT was greater than that for GXT. The GXTs were primarily used by one group ( Massett and Berk, 2005 ; Avila et al, 2017 ; Kim et al, 2020 ) and all the study protocols were 4weeks in length. In contrast, average training duration in studies utilizing ILT protocols was 7.4±2.8weeks.…”

Characterization of the blood–brain barrier in genetically diverse laboratory mouse strains

“…Experimental models of cardiovascular disease or adaptation to exercise largely depend on genetic background and differences in endothelial function (e.g. ACh dose–response curves) [ 7 , 8 ]. In the CNS, inbred mouse strains show differences in neurogenesis [ 9 – 11 ], in behavioral performance [ 12 ], ischemic stroke volume [ 13 ], regenerative capacities [ 14 ], and cerebral collateral vessel density [ 15 ].…”