PS 07-30 AGE-ASSOCIATED CHANGES IN THE VASCULAR RENIN-ANGIOTENSIN-SYSTEM IN MICE

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Abstract

Objective:

This study evaluated whether the change in the renin-angiotensin system (RAS) is associated with arterial aging in mice.

Design and Method:

Histologic changes and expressions of transforming growth factor-β (TGF-β), collagen IV, angiotensin II (Ang II), angiotensin converting enzyme (ACE), angiotensin converting enzyme 2 (ACE2), angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), prorenin receptor (PRR), Mas receptor (MasR), endothelial nitric oxide synthase (eNOS), NADPH oxidase 2 and 4 (Nox2 and Nox4), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and superoxide dismutase 1 and 2 (SOD1 and SOD2), were measured in the thoracic aortas from 2-month-old, 12-month-old, and 24-month-old C57/BL6 mice.

Results:

Twenty-four-month-old mice showed significantly increased aortic media thickness and expressions of TGF-β and collagen IV compared to 2-month-old and 12-month-old mice. The expressions of PRR, ACE, and Ang II, and AT1R-positive area significantly increased, whereas expressions of ACE2 and MasR and AT2R-positive area decreased with age. The expressions of phosphorylated eNOS, SOD1 and SOD2 decreased, and the 8-OHdG-positive area increased with age. The expression of Nox2 significantly increased with age, but that of Nox4 did not change.

Conclusions:

The enhanced PRR-ACE-Ang II-AT1R axis and reduced ACE2-MasR axis were associated arterial aging in mice.

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