Changes in the structure-function relationship of elastin and its impact on the proximal pulmonary arterial mechanics of hypertensive calves

Abstract

Extracellular matrix remodeling has been proposed as one mechanism by which proximal pulmonary arteries stiffen during pulmonary arterial hypertension (PAH). Although some attention has been paid to the role of collagen and metallomatrix proteins in affecting vascular stiffness, much less work has been performed on changes in elastin structure-function relationships in PAH. Such work is warranted, given the importance of elastin as the structural protein primarily responsible for the passive elastic behavior of these conduit arteries. Here, we study structure-function relationships of fresh arterial tissue and purified arterial elastin from the main, left, and right pulmonary artery branches of normotensive and hypoxia-induced pulmonary hypertensive neonatal calves. PAH resulted in an average 81 and 72% increase in stiffness of fresh and digested tissue, respectively. Increase in stiffness appears most attributable to elevated elastic modulus, which increased 46 and 65%, respectively, for fresh and digested tissue. Comparison between fresh and digested tissues shows that, at 35% strain, a minimum of 48% of the arterial load is carried by elastin, and a minimum of 43% of the change in stiffness of arterial tissue is due to the change in elastin stiffness. Analysis of the stress-strain behavior revealed that PAH causes an increase in the strains associated with the physiological pressure range but had no effect on the strain of transition from elastin-dominant to collagen-dominant behavior. These results indicate that mechanobiological adaptations of the continuum and geometric properties of elastin, in response to PAH, significantly elevate the circumferential stiffness of proximal pulmonary arterial tissue.

Cellular, Pharmacological, and Biophysical Evaluation of Explanted Lungs from a Patient with Sickle Cell Disease and Severe Pulmonary Arterial Hypertension

“…27 This allows for the tissue to move freely in both directions, circumferential and longitudinal. The strain was measured optically by software that keeps track of the relative distance between the black dots on the sample (optical markers).…”

The role of collagen in extralobar pulmonary artery stiffening in response to hypoxia-induced pulmonary hypertension

“…biomechanics; mechanobiology; elastin; hydroxyproline; recovery HYPOXIC PULMONARY HYPERTENSION (HPH) is caused by living at high altitudes and is a complication of many lung diseases, including chronic obstructive pulmonary disease (1, 13, 16), cystic fibrosis (10), and obstructive sleep apnea (13), which contributes significantly to morbidity and mortality. Pulmonary vascular remodeling due to chronic HPH increases conduit pulmonary artery (PA) stiffness (4,20,21,23,34,42). Conduit PA stiffening likely increases wave reflections to impair right ventricular systolic function, much like aortic stiffening impairs left ventricular systolic function (18,29,33).…”

“…Our laboratory has previously shown that HPH increases wave reflections in the mouse pulmonary circulation (44). Recent evidence showing that conduit PA stiffness is a strong predictor of mortality in PA hypertension (12, 30) further supports the importance of PA stiffness to pulmonary and right ventricular function.The dominant morphological changes in conduit PAs in response to HPH are accumulation of collagen and elastin (20, 21) and wall thickening (4,20,21,23). Stiffening of the extralobar PAs has been shown to be linked with accumulation of collagen and elastin (4,20,21,23,42).…”

“…Pulmonary vascular remodeling due to chronic HPH increases conduit pulmonary artery (PA) stiffness (4,20,21,23,34,42). Conduit PA stiffening likely increases wave reflections to impair right ventricular systolic function, much like aortic stiffening impairs left ventricular systolic function (18,29,33).…”

“…Stiffening of the extralobar PAs has been shown to be linked with accumulation of collagen and elastin (4,20,21,23,42). Previous attempts to understand the individual roles of collagen and elastin in arterial mechanical function have focused on correlative relationships during HPH progression (20,21) or ex vivo degradation of one component before mechanical testing (23). A disadvantage of the first approach is that, if elastin also increases during HPH progression, the impact of either protein alone cannot be discerned; a disadvantage of the second approach is that degradation of one component may alter potentially important interactions between the two (9).…”