Details

Autor(en) / Beteiligte

• De Munck, Dorien G.
• Leloup, Arthur J.A.
• De Meyer, Guido R. Y.
• Martinet, Wim
• Fransen, Paul

Titel

Defective autophagy in vascular smooth muscle cells increases passive stiffness of the mouse aortic vessel wall

Ist Teil von

• Pflügers Archiv, 2020-08, Vol.472 (8), p.1031-1040

Ort / Verlag

Berlin/Heidelberg: Springer Berlin Heidelberg

Erscheinungsjahr

2020

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Aging and associated progressive arterial stiffening are both important predictors for the development of cardiovascular diseases. Recent evidence showed that autophagy, a catabolic cellular mechanism responsible for nutrient recycling, plays a major role in the physiology of vascular cells such as endothelial cells and vascular smooth muscle cells (VSMCs). Moreover, several autophagy inducing compounds are effective in treating arterial stiffness. Yet, a direct link between VSMC autophagy and arterial stiffness remains largely unidentified. Therefore, we investigated the effects of a VSMC-specific deletion of the essential autophagy-related gene Atg7 in young mice (3.5 months) (Atg7 F/F SM22α-Cre + mice) on the biomechanical properties of the aorta, using an in-house developed Rodent Oscillatory Tension Set-up to study Arterial Compliance (ROTSAC). Aortic segments of Atg7 F/F SM22α-Cre + mice displayed attenuated compliance and higher arterial stiffness, which was more evident at higher distention pressures. Passive aortic wall remodeling, rather than differences in VSMC tone, is responsible for these phenomena, since differences in compliance and stiffness between Atg7 +/+ SM22α-Cre + and Atg7 F/F SM22α-Cre + aortas were more pronounced when VSMCs were completely relaxed by the addition of exogenous nitric oxide. These observations are supported by histological data showing a 13% increase in medial wall thickness and a 14% decrease in elastin along with elevated elastin fragmentation. In addition, expression of the calcium-binding protein S100A4, which is linked to matrix remodeling, was elevated in aortic segments of Atg7 F/F SM22α-Cre + mice. Overall, these findings illustrate that autophagy exerts a crucial role in defining arterial wall compliance.