Proximal Pulmonary Artery Stiffening as a Biomarker of Cardiopulmonary Aging

TL;DR

This study shows that stiffening of the proximal pulmonary artery is a sign of aging and may lead to reduced lung and heart function.

Contribution

The study identifies proximal pulmonary artery stiffening and collagen reorientation as novel biomarkers of cardiopulmonary aging.

Findings

Aging leads to increased circumferential stiffness of the proximal pulmonary artery and collagen reorientation.

Transcriptional changes in aging arteries suggest senescence and increased ECM turnover involving TGFβ signaling.

Stiffened arteries correlate with decreased lung and right ventricle function in multiple aging mouse models.

Abstract

The geroscience hypothesis suggests that understanding mechanisms underlying aging will enable us to delay and lessen age‐related disability and diseases. The role of mechanical factors has been increasingly appreciated in many aspects of the aging process. Here, we use mouse models to investigate changes in the biomechanics of the proximal pulmonary artery, lung function, and right ventricle function in aging. We found an age‐related decreased capacity to store energy and increased circumferential stiffness of the proximal pulmonary artery with age that is associated with a reorientation of collagen toward the circumferential direction, decreased exercise ability, and decreased function of the lung and right ventricle. The observed compromised mechanics in the proximal pulmonary artery are consistent across multiple mouse models of accelerated aging. Furthermore, transcriptional changes in the proximal pulmonary artery indicate that aging is associated with senescence of perivascular macrophages, adventitial fibroblasts, and medial smooth muscle cells. Older pulmonary arteries increase expression of genes associated with ECM turnover (including genes in the TGFβ pathway) and increased intercellular signaling amongst perivascular macrophages, fibroblasts, and smooth muscle cells. Our results provide promising biomarkers of aging for diagnosis and potential pathways and molecular targets for antiaging therapies.

Mouse models revealed age‐associated increased circumferential stiffness of the proximal pulmonary artery that was associated with reorientation of collagen and decreased function of the lung and right ventricle. Age‐related transcriptional changes were indicative of senescence, ECM turnover, TGFβ signaling, and altered intercellular signaling among perivascular macrophages, fibroblasts, and smooth muscle cells.

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