Cardioprotection by spermidine does not depend on structural characteristics of the myocardial microcirculation in aged mice.

Aims: Ageing is associated with cardiovascular disease and reduced cardiac function. This cardiac functional decline is accompanied by cardiac remodeling and alterations in cardiomyocyte composition. Recently, it was shown that the natural polyamine spermidine preserves cardiac function and cardiomyocyte composition in old mice. As cardiac function critically relies on blood supply, we tested whether spermidine has also beneficial effects on ageing-associated changes of the myocardial microcirculation.

Methods: Using transmission electron microscopy, the left ventricular capillaries of young (4-months old) and aged (24-months old) C57BL/6J male mice were investigated by stereology. Aged mice were subdivided into an untreated group and a group that was fed spermidine late in life for 6 months. Specifically, total volume, surface area and length of capillaries as well as endothelial thickness were estimated. Additionally, the total length of precapillary arterioles was assessed. The protein level of VEGF-A was measured using Western blot.

Results: Ageing was associated with whole heart and left ventricular hypertrophy. All total capillary-related values (including volume, surface area and length) were significantly higher in 24-month-old mice compared with 4-month-old mice. Moreover, VEGF-A expression was significantly enhanced in aged mice. The mean thickness of the endothelium was not different, but the mean area of myocardium supplied by capillaries was smaller in old mice. Spermidine treatment had no significant effect on the ageing-associated structural changes or VEGF-A expression.

Conclusions: In conclusion, in the left ventricles of aged mice the growth of capillaries and arterioles supplying cardiomyocytes were in proportion to whole organ hypertrophy. Spermidine had no effect on quantitative characteristics of capillaries or arterioles, suggesting that the beneficial effects of spermidine on the ageing heart do not depend on the quantitative structural characteristics of the microcirculation which does not exclude potential functional differences between the groups.