Assessing Murine Aortic Intrinsic Stiffness Using Pin Myography: A Translational Framework For Interrogating The Influence of the Circulating Milieu.

摘要

Aortic stiffening is an independent risk factor for cardiovascular disease and other chronic conditions, including cognitive decline, kidney dysfunction, vision impairment, and reduced glucose-insulin function. In vivo, aortic stiffness is commonly assessed using tonometry- or ultrasound-based techniques that visualize arterial waveforms or longitudinal arterial segments, respectively. However, in vivo measurements are influenced by multiple factors-such as arterial pressure and autonomic input-which limit mechanistic insight into how and why aortic stiffness changes. Preclinical murine models, which permit direct acquisition of aortic tissue, offer a unique experimental framework to assess both in vivo aortic stiffness and the intrinsic mechanical properties of the aorta, free from confounding physiological variables. These models also enable direct interrogation of the circulating milieu (i.e., collection of circulating bioactive molecules in the bloodstream) and its role in modulating aortic stiffness across the preclinical-to-clinical translational spectrum. Alterations in the circulating milieu have emerged as a key mechanistic underpinning of aortic stiffening in numerous conditions-including primary aging and premature aging associated with cancer and cancer therapies-across both preclinical and clinical studies, as well as in mediating the effects of interventions. This article provides a step-by-step guide for assessing: (1) intrinsic aortic stiffness (elastic modulus) in preclinical murine models, and (2) the contribution of the circulating milieu (and its constituents) to aortic stiffening using both preclinical and clinical biospecimens.