Age-related changes to cerebral artery stiffness and structure in mice

Abstract

Introduction: With advancing age, there are changes in the structural and material properties of the arterial wall. While the age-related increase in stiffness is well described for large arteries, less is known about the structural changes to cerebral arteries with age. In response to increased blood pressure, as occurs with aging, arteries typically undergo remodeling that includes smooth muscle cell proliferation and collagen accumulation. This remodeling contributes to increased stiffness and reduces pulse pressure dampening, potentially leading to damage to arterioles and capillaries. We hypothesized that old cerebral arteries would display greater stiffness, wall thickness, collagen content, and smooth muscle content compared with young cerebral arteries. Methods: We studied old male (n=10, 24-27 months) and young male (n=9, 4-7 months) C57BL/6 mice. For measures of stiffness, isolated posterior cerebral arteries were exposed to pulsatile pressure (37.5 to 87.5 mmHg, 400 pulses/min) for 30 minutes. Artery diameters during the pulsation were recorded and used to calculate distension, β-stiffness index, and Peterson modulus of elasticity (EP). In sections of the middle cerebral arteries, total wall thickness and total collagen were measured in Masson’s trichrome-stained arteries. Collagen-1 and α-smooth muscle actin content were measured by immunofluorescence in middle cerebral artery sections. Data were analyzed by a Shapiro-Wilks test for normality, and young and old groups were compared by student’s t-test. Group comparisons for β-stiffness, EP, and percent change in diameter were made using a Mann-Whitney test. A p<0.05 was considered statistically significant. Data are mean±SD. Results: Cerebral arteries from young mice, compared with old mice, had a higher distensibility during the application of pulsatile pressure, measured by the percent change in diameter (8.0±4.0% vs. 5.1±2.5%, p=0.03) or absolute change in diameter (12.0±5.4 μm vs. 7.8±3.8 μm, p=0.03). Cerebral artery stiffness, calculated by β-stiffness index (13.1±6.5 AU vs. 21.9±13.8 AU, p=0.03) and EP (777±384 kPa 102 vs.1293±816 kPa 102, p=0.03) was lower in young mice compared with old mice. There was no difference in cerebral artery wall thickness between groups (6.9±3.0 μm vs. 9.6±2.3 μm, p=0.08). Cerebral arteries from old mice had greater amounts of α-smooth muscle actin compared to young mice (1.4±0.2 AU vs. 1.0±0.2 AU, p=0.009). Interestingly, cerebral arteries from old mice had lower collagen-1 compared to young mice (0.8±0.1 vs. 1.0±0.1 AU, p=0.01), but the opposite trend was observed for total collagen (26.3±13.6 AU vs. 17.6±9.6, p=0.06). Conclusion: These results demonstrate that advancing age results in increased functional stiffness of cerebral arteries. An age-related increase in smooth muscle is a potential cause of higher cerebral artery stiffness. This project was funded by NIH R01 AG064016 and the Oregon Medical Research Foundation. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.