Functional and structural changes in aorta of mice divergently selected for basal metabolic rate

Abstract

Cardiovascular diseases (CVD) are one of the most common causes of mortality likely genetically linked to the variation in basal metabolic rate (BMR). A robust test of the significance of such association may be provided by artificial selection experiments on animals selected for diversification of BMR. Here we asked whether genetically determined differences in BMR correlate with anatomical shift in endothelium structure and if so, the relaxation and contraction responses of the aorta in mice from two lines of Swiss-Webster laboratory mice (Mus musculus) divergently selected for high or low BMR (HBMR and LBMR lines, respectively). Functional and structural study of aorta showed that a selection for divergent BMR resulted in the between-line difference in diastolic aortic capacity. The relaxation was stronger in aorta of the HBMR mice, which may stem from greater flexibility of aorta mediated by higher activity of Ca 2+ -activated K + channels. Structural examination also indicated that HBMR mice had significantly thicker aorta's middle layer compared to LBMR animals. Such changes may promote arterial stiffness predisposing to cardiovascular diseases. BMR-related differences in the structure and relaxation ability of aortas in studied animals may be reminiscent of potential risk factors in the development of CVD in humans.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Nitric oxide, endothelium‐derived hyperpolarizing factor, and smooth muscle‐dependent mechanisms contribute to magnesium‐dependent vascular relaxation in mouse arteries

“…36,82 This mechanism of vasodilation is more pronounced in small resistance vessels than in large conduit vessels. 43,54 However, the expression of IK Ca and SK Ca channels, [83][84][85][86] as well as a functional contribution of EDHF to Ach-induced relaxation, has been shown in rodent aorta. [87][88][89][90] In the current study, blocking IK Ca and SK Ca channels with the combination of apamin and TRAM34 reduced Mg 2+ -induced relaxation in mouse aorta.…”

The association between the basal metabolic rate and cardiovascular disease: A two‐sample Mendelian randomization study

“…[31][32][33] It has also been reported that BMR is associated with the pro-inflammatory state 34,35 and immune activation in the organism as a whole, 36 and there is a positive correlation between BMR and the pro-inflammatory state in normal and overweight people. 7 Second, there is also relevant anatomical evidence that in mice with high BMR, the probability of intimal thickening, arteriosclerosis and myocyte degradation is increased, 37 which is an important mechanism of cardiovascular diseases. 38 A recent Mendelian study revealed an association between BMR and various cardiovascular conditions, such as aortic aneurysm, atrial flutter and heart failure.…”

Causal Effects of Basal Metabolic Rate on Cardiovascular Disease: A Bidirectional Mendelian Randomization Study

“…In addition, BMR was significantly correlated with aortic diastolic capacity. 30 It has been proven that BMR is associated with increased hypertension and that elevated myocardial oxygen consumption increases the burden on the heart. 9 It appears that increased BMR may act as a potential risk factor for the development of CVDs in humans.…”