Abstract Body: Objective: The risk of developing hypertensive cardiovascular diseases increases with age. Gut microbiota play a vital role in maintaining cardiovascular health by producing short-chain fatty acids (SCFAs), such as propionate (C3), which protects against cardiovascular damage. Therefore, the aim of this study is to investigate the effects of propionate on hypertensive cardiovascular damage during aging.
Design and Methods: Male C57BL/6J mice (8-12 weeks old) were fed a low-fiber diet and 200 mM Na-propionate or a control solution in drinking water for six weeks (young mice) or eight months (middle-aged mice). In the last four weeks of each experimental period, hypertension was induced in the mice by angiotensin II (400 ng/kg/min via osmotic minipumps). The flow-mediated vasodilation (FMD) method was used to assess endothelial function in-vivo. At the end of the study, the heart was collected for ex-vivo analyses.
Results: C3 treatment led to a significant reduction in cardiac hypertrophy indices in hypertensive middle-aged mice [M±SEM: 9.29±0.14 mg/mm vs. 10.55±0.19 mg/mm (n=20)], no effect was observed in young mice [M±SEM: 8.29±0.22 mg/mm vs. 8.74±0.23 mg/mm (n=19-20)]. In middle-aged mice, C3 treatment significantly reduced the cardiac expression of fibrotic markers (Col1a1, Col3a1, and Fn1), but showed no effect in young animals. Moreover, gene expression of the pro-inflammatory cytokine IL-1β and the chemokine CCL3 were decreased in middle-aged mice treated with C3, whereas no differences were observed in young mice. FMD measurements revealed that C3 treatment had no effect on endothelial function in either young or middle-aged hypertensive mice. However, endothelial function significantly deteriorated with age in the control group, but not in the C3-treated group.
Conclusion: Our results demonstrate that C3 exerts protective effects against hypertensive cardiovascular damage during aging. It is associated with reduced cardiac inflammation and fibrosis and preserved endothelial function during aging.