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1. A topological data analysis study on murine pulmonary arterial trees with pulmonary hypertension

   https://doi.org/10.1016/j.mbs.2023.109056  

   Miller, Megan; Johnston, Natalie; Livengood, Ian; Spinelli, Miya; Sazdanovic, Radmila; Olufsen, Mette S. (October 2023, Mathematical Biosciences)

   Pulmonary hypertension (PH), defined by a mean pulmonary arterial blood pressure above 20 mmHg in the main pulmonary artery, is a cardiovascular disease impacting the pulmonary vasculature. PH is accompanied by chronic vascular remodeling, wherein vessels become stiffer, large vessels dilate, and smaller vessels constrict. Some types of PH, including hypoxia-induced PH (HPH), also lead to microvascular rarefaction. This study analyzes the change in pulmonary arterial morphometry in the presence of HPH using novel methods from topological data analysis (TDA). We employ persistent homology to quantify arterial morphometry for control and HPH mice characterizing normalized arterial trees extracted from micro-computed tomography (micro-CT) images. We normalize generated trees using three pruning algorithms before comparing the topology of control and HPH trees. This proof-of-concept study shows that the pruning method affects the spatial tree statistics and complexity. We find that HPH trees are stiffer than control trees but have more branches and a higher depth. Relative directional complexities are lower in HPH animals in the right, ventral, and posterior directions. For the radius pruned trees, this difference is more significant at lower perfusion pressures enabling analysis of remodeling of larger vessels. At higher pressures, the arterial networks include more distal vessels. Results show that the right, ventral, and posterior relative directional complexities increase in HPH trees, indicating the remodeling of distal vessels in these directions. Strahler order pruning enables us to generate trees of comparable size, and results, at all pressure, show that HPH trees have lower complexity than the control trees. Our analysis is based on data from 6 animals (3 control and 3 HPH mice), and even though our analysis is performed in a small dataset, this study provides a framework and proof-of-concept for analyzing properties of biological trees using tools from Topological Data Analysis (TDA). Findings derived from this study bring us a step closer to extracting relevant information for quantifying remodeling in HPH. 

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2. Pulmonary Surfactant: A Mighty Thin Film

   https://doi.org/10.1021/acs.chemrev.3c00146  

   Possmayer, Fred; Zuo, Yi Y; Veldhuizen, Ruud_A W; Petersen, Nils O (December 2023, Chemical Reviews)
3. The biophysical function of pulmonary surfactant

   https://doi.org/10.1016/j.bpj.2024.04.021  

   Hall, Stephen B; Zuo, Yi Y (June 2024, Biophysical Journal)
4. Cellular mechanosignaling in pulmonary arterial hypertension

   https://doi.org/10.1007/s12551-021-00828-3  

   Wang, Ariel; Valdez-Jasso, Daniela (October 2021, Biophysical Reviews)

   Abstract Pulmonary arterial hypertension (PAH) is a vasculopathy characterized by sustained elevated pulmonary arterial pressures in which the pulmonary vasculature undergoes significant structural and functional remodeling. To better understand disease mechanisms, in this review article we highlight recent insights into the regulation of pulmonary arterial cells by mechanical cues associated with PAH. Specifically, the mechanobiology of pulmonary arterial endothelial cells (PAECs), smooth muscle cells (PASMCs) and adventitial fibroblasts (PAAFs) has been investigated in vivo, in vitro, and in silico. Increased pulmonary arterial pressure increases vessel wall stress and strain and endothelial fluid shear stress. These mechanical cues promote vasoconstriction and fibrosis that contribute further to hypertension and alter the mechanical milieu and regulation of pulmonary arterial cells. 

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5. Biomimetic human small muscular pulmonary arteries

   https://doi.org/10.1126/sciadv.aaz2598  

   Jin, Qianru; Bhatta, Anil; Pagaduan, Jayson V.; Chen, Xing; West-Foyle, Hoku; Liu, Jiayu; Hou, Annie; Berkowitz, Dan; Kuo, Scot C.; Askin, Frederic B.; et al (March 2020, Science Advances)

   Changes in structure and function of small muscular arteries play a major role in the pathophysiology of pulmonary hypertension, a burgeoning public health challenge. Improved anatomically mimetic in vitro models of these microvessels are urgently needed because nonhuman vessels and previous models do not accurately recapitulate the microenvironment and architecture of the human microvascular wall. Here, we describe parallel biofabrication of photopatterned self-rolled biomimetic pulmonary arterial microvessels of tunable size and infrastructure. These microvessels feature anatomically accurate layering and patterning of aligned human smooth muscle cells, extracellular matrix, and endothelial cells and exhibit notable increases in endothelial longevity and nitric oxide production. Computational image processing yielded high-resolution 3D perspectives of cells and proteins. Our studies provide a new paradigm for engineering multicellular tissues with precise 3D spatial positioning of multiple constituents in planar moieties, providing a biomimetic platform for investigation of microvascular pathobiology in human disease. 

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