Progressive aortic stiffness in aging C57Bl/6 mice displays altered contractile behaviour and extracellular matrix changes

• Published in: Communications biology Vol. 5; no. 1; p. 605
• Main Authors: De Moudt, Sofie, Hendrickx, Jhana O., Neutel, Cédric, De Munck, Dorien, Leloup, Arthur, De Meyer, Guido R. Y., Martinet, Wim, Fransen, Paul
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.06.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/51; 45/77; 631/443/592/75/593/2724; 631/443/7; 631/80/304; 631/80/86/1999; 64/60; 96/63; Aging; Aorta; Biology; Biomedical and Life Sciences; Blood pressure; Calcium channels (voltage-gated); Cardiovascular disease; Cardiovascular diseases; Cell signaling; Echocardiography; Extracellular matrix; Hypertrophy; Life Sciences; Muscle contraction; Peripheral blood; Smooth muscle
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-022-03563-x

Aortic stiffness is a hallmark of cardiovascular disease, but its pathophysiology remains incompletely understood. This study presents an in-dept characterization of aortic aging in male C57Bl/6 mice (2–24 months). Cardiovascular measurements include echocardiography, blood pressure measurement, and ex vivo organ chamber experiments. In vivo and ex vivo aortic stiffness increases with age, and precede the development of cardiac hypertrophy and peripheral blood pressure alterations. Contraction-independent stiffening (due to extracellular matrix changes) is pressure-dependent. Contraction-dependent aortic stiffening develops through heightened α 1 -adrenergic contractility, aberrant voltage-gated calcium channel function, and altered vascular smooth muscle cell calcium handling. Endothelial dysfunction is limited to a modest decrease in sensitivity to acetylcholine-induced relaxation with age. Our findings demonstrate that progressive arterial stiffening in C57Bl/6 mice precedes associated cardiovascular disease. Aortic aging is due to changes in extracellular matrix and vascular smooth muscle cell signalling, and not to altered endothelial function. A 24-month aging study in male C57Bl/6 mice reveals that aortic aging precedes cardiovascular disease and is due to changes in the extracellular matrix and vascular smooth muscle cell signaling.