OS 15-09 DOES ACE2-ANGIOTENSIN-(1–7) AXIS PROTECT FROM AGING-ASSOCIATED LOSS OF SKELETAL MUSCLE FUNCTION?

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Abstract

Objective:

Angiotensin converting enzyme2 (ACE2), an enzyme that produces the Angiotensin 1–7(A1–7) from Angiotensin II, is considered to suppress organ damage by inhibition of the activation of renin-angiotensin system. We recently found that ACE2 deficiency in mice ameliorated insulin sensitivity of skeletal muscle with reduced expression of glucose transporter 4 and myocyte enhancer factor 2, an important transcription factor to maintain homeostasis of skeletal muscle. In this study, we investigated whether ACE2-A1–7 axis plays a protective role in aging-associated loss of skeletal muscle function in mice.

Design and Method:

To assess serial change in motor function, we performed grip strength test in 3, 6, 12, 18, and 24 month old wildtype and ACE2 knockout (KO) mice. Grip strength at each period was calculated by average of 12 times measurements (6 times for 2days). At 24 month old, saline or A1–7 (100ng / kg / min) was administered for 4 weeks by osmotic mini pumps and grip strength was compared before and after administration.

Results:

At 3 months, there was no significant difference in grip strength between ACE2KO and wildtype mice. While grip strength of wildtype mice remained unchanged until 18 month old, ACE2KO mice reduced their grip strength after 6 month old. Wildtype mice reduced grip strength at 24 month, but the difference in grip strength between wildtype and ACE2KO mice was still observed. Administration of A1–7 at 24 month old mice significantly improved loss of grip strength in wildtype and ACE2KO mice. There was no difference in grip strength between A1–7-administrated wildtype and ACE2KO mice. There was no difference in weight and size of skeletal muscle of lower limbs between wildtype and ACE2KO mice at 24 months.

Conclusions:

ACE2-Angiotensin(1–7) axis may protect from age-associated loss of skeletal muscle function without no obvious alternation in muscle mass.

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