Hesperidin reverses perivascular adipose-mediated aortic stiffness with aging

We tested the hypothesis that hesperidin would reverse age-related aortic stiffness, perivascular adipose (PVAT) mediated-arterial stiffening and PVAT advanced glycation end-products (AGE) accumulation. Aortic pulse wave velocity (aPWV) and intrinsic mechanical stiffness, two measures of arterial stiffness, were assessed in C57BL/6 mice that were young (6 months), old (27–29 months), or old treated with hesperidin for 4 weeks. Old compared with young mice had increased aPWV (444 ± 10 vs. 358 ± 8 cm/s, P < 0.05) and mechanical stiffness (6506 ± 369 vs. 3664 ± 414 kPa, P < 0.05). In old mice hesperidin reduced both aPWV (331 ± 38 cm/s) and mechanical stiffness (4445 ± 667 kPa) to levels not different from young. Aortic segments from old animals cultured with (+) PVAT had greater mechanical stiffness compared to young (+) PVAT (6454 ± 323 vs. 3575 ± 440 kPa, P < 0.05) that was ameliorated in arteries from old hesperidin treated cultured (+) PVAT (2639 ± 258 kPa). Hesperidin also reversed the aging-related PVAT AGE accumulation (all, P < 0.05). A 4-week treatment with the AGE inhibitor aminoguanidine reversed both the age-related increase in aPWV (390 ± 7 cm/s) and mechanical stiffness (3396 ± 1072 kPa), as well as mechanical stiffness in arteries cultured (+) PVAT (3292 ± 716 kPa) (all, P < 0.05) to values not different from young. In conclusion, hesperidin ameliorates the age-related increase in aortic stiffness and the PVAT-mediated effects on arterial stiffening. Hesperidin also reversed PVAT AGE accumulation, where PVAT AGE were shown to promote aortic stiffness with aging.