Potential role of a disintegrin and metalloproteinase-17 (ADAM17) in age-associated ventricular remodeling of rats.

Excessive tumor necrosis factor-α (TNF-α) could enhance cell death and aggravate left ventricular remodeling and myocardial dysfunction. A disintegrin and metalloproteinase-17 (ADAM17), an important maturation regulator of TNF-α, might be involved in the aging-associated ventricular remodeling. The present study observed myocardial ADAM17 expression in young and aged rats and explored the association between cardiac structure/function and expression of ADAM17 in 6 month-old ( n = 10, young group) and 24 month-old SD rats ( n = 10, old group). The body, heart weight and heart weight/body weight ratio of rats in the old group were all significantly increased compared to that in the young group ( P < 0.05). The left ventricular systolic end-diameter and end-diastolic diameters were significantly enlarged in the old group compared to the young group ( P < 0.05), while the systolic function index including the left ventricular ejection fraction and left ventricular fractional shortening were similar between the two groups. The peak mitral flow velocity ( E )/peak mitral annulus velocity ( E ') ratio was significantly higher in the old group than in the young group ( P < 0.05). Histological examination showed more damage of cardiomyocytes, interstitial collagen deposition and inflammatory cell infiltration in the old group. Immunohistochemistry examination showed that myocardial TNF-α expression was mainly located in cardiomyocytes and was significantly higher in the old group than in the young group ( P < 0.05). The protein expression of myocardial ADAM17 detected by western blot was significantly higher in the old group than in the young group ( P < 0.05), while TIMP-3 expression was similar between the two groups. The present study suggested that ADAM17 and inflammation might play an important role in aging-related myocardial remodeling through regulating TNF-α.