Dichotomous mechanisms of aortic stiffening in high‐fat diet fed young and old B6D2F1 mice

Abstract Advancing age is associated with increased stiffness of large elastic arteries as assessed by aortic pulse wave velocity (PWV). Greater PWV, associated with increased risk of cardiovascular diseases, may result from altered expression of the extracellular matrix proteins, collagen and elastin, as well as cross-linking of proteins by advanced glycation end products (AGEs). Indeed, aortic PWV is greater in old (28-31 months) normal chow (NC, 16% fat by kcal)-fed male B6D2F1 mice compared with young (Y: 5-7 months) NC-fed mice (397 ± 8 vs. 324 ± 14 cm/s, P < 0.05). Aging also induces a ~120% increase in total aortic collagen content assessed by picosirius red stain, a ~40% reduction in medial elastin assessed by Verhoeff's Van Geison stain, as well as a 90% greater abundance of AGEs in the aorta (P < 0.05). The typical American diet contains high dietary fat and may contribute to the etiology of arterial stiffening. To that end, we hypothesized that the age-associated detriments in arterial stiffening are exacerbated in the face of high dietary fat. In young animals, high-fat (40% fat by kcal) diet increases aortic stiffness by 120 ± 18 cm/s relative to age-matched NC-fed mice (P < 0.001). High-fat was without effect on aortic collagen or AGEs content in young animals; however, elastin was greatly reduced (~30%) after high-fat in young mice. In old animals, high-fat increased aortic stiffness by 108 ± 47 cm/s but was without effect on total collagen content, medial elastin, or AGEs. These data demonstrate that both aging and high-fat diet increase aortic stiffness, and although a reduction in medial elastin may underlie increased stiffness in young mice, stiffening of the aorta in old mice after high-fat diet does not appear to result from a similar structural modification.