PT  - JOURNAL ARTICLE
AU  - Danial Sharifi Kia
AU  - Yuanjun Shen
AU  - Timothy N. Bachman
AU  - Elena A. Goncharova
AU  - Kang Kim
AU  - Marc A. Simon
TI  - Effects of Healthy Aging on Right Ventricular Structure and Biomechanical Properties
AID  - 10.1101/2020.09.08.288332
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.08.288332
4099  - http://biorxiv.org/content/early/2020/09/09/2020.09.08.288332.short
4100  - http://biorxiv.org/content/early/2020/09/09/2020.09.08.288332.full
AB  - Healthy aging has been associated with alterations in pulmonary vasculature and right ventricular (RV) hemodynamics, potentially leading to RV remodeling. Despite the current evidence suggesting an association between aging and alterations in RV function and higher prevalence of pulmonary hypertension in the elderly, limited data exist on age-related differences in RV structure and biomechanics. In this work we report our preliminary findings on the effects of healthy aging on RV structure, function, and biomechanical properties. Hemodynamic measurements, biaxial mechanical testing, constitutive modeling, and quantitative histological analysis were employed to study two groups of Sprague-Dawley rats: control (11 weeks) and aging (80 weeks).Aging was associated with increases in RV peak pressures (≈↑17%, p=0.017), RV contractility (≈↑52%, p= 0.004), and RV wall thickness (≈↑34%, p=0.002). Longitudinal realignment of RV collagen (16.4°, p=0.013) and myofibers (14.6°, p=0.017) were observed with aging, accompanied by transmural cardiomyocyte loss and fibrosis. A bimodal alteration in biomechanical properties was noted, resulting in increased myofiber stiffness (≈↑158%, p=0.0006) and decreased effective collagen fiber stiffness (≈↓67%, p=0.031).Our results demonstrate the potential of healthy aging to modulate RV remodeling via increased peak pressures, cardiomyocyte loss, fiber reorientation, and altered collagen/myofiber stiffness. Some similarities were observed between aging-induced remodeling patterns and those of RV remodeling in pressure overload.Competing Interest StatementD.S.K: None, Y.S: None, T.N.B: None, E.A.G: None, K.K: None, M.A.S: Research support from Novartis, Aadi. Consultancy fees from Complexa, Actelion, United Therapeutics, Acceleron