Perivascular adipose tissue in age‐associated arterial stiffening: Role of transforming growth factor beta 1

Aging causes large elastic artery stiffening associated with adventitial myofibroblast‐related increases in transforming growth factor beta 1 (TGF‐β1), collagen I and advanced glycation end‐products (AGEs). We tested the hypothesis that perivascular adipose tissue (PVAT) from older animals induces these protein changes in adventitial fibroblasts (AFB) and that the increase in TGF‐β1 causes arterial stiffening. AFB cultured from old (O, 24 mo, n=3–6) vs. young (Y, 6 mo, n=4–6) male Sprague Dawley rats had greater (p<0.05) smooth muscle alpha actin (SMαA, 1.92 ± 0.21 vs. 1.00 ± 0.08), a marker of myofibroblasts, TGF‐β1 (15.77 ± 1.13 vs. 1.00 ± 0.21), collagen I (1.71 ±0.04 vs. 1.00 ± 0.14) and AGEs (4.49 ± 1.69 vs. 1.00 ± 0.20). In AFB from Y, PVAT from O rats increased (p < 0.05) SMαA (1.76 ± 0.18), TGF‐β1 (7.28 ± 1.98) and collagen I (1.58 ± 0.21), but not AGEs (1.12 ± 0.38), and TGF‐β1 treatment mimicked these changes (SMαA: 1.00 ± 0.14 to 3.00 ± 0.44 and collagen I: 1.00 ± 0.04 to 1.71 ± 0.14, both p < 0.05; AGEs: 1.00 ± 0.04 vs. 0.91 ± 0.22). Arterial stiffness (aortic pulse wave velocity, aPWV) was greater (p < 0.05) in O (26–27 mo, n=5) vs. Y (4–6 mo, n=5) male C57Bl/6N mice (469 ± 16 vs. 351 ± 13) and 6‐week direct arterial application of recombinant TGF‐β1 to the aorta in vivo increased (p<0.05) aPWV in Y (417 ± 6). These results suggest that PVAT may contribute to age‐associated arterial stiffening via TGF‐β1.