scholarly journals Three-Dimensional Micro Computed Tomography Analysis of the Lung Vasculature and Differential Adipose Proteomics in the Sugen/Hypoxia Rat Model of Pulmonary Arterial Hypertension

2016 ◽  
Vol 6 (4) ◽  
pp. 586-596 ◽  
Author(s):  
Kelly J. Shields ◽  
Kostas Verdelis ◽  
Michael J. Passineau ◽  
Erin M. Faight ◽  
Lee Zourelias ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Adipose Tissue ◽  
Pulmonary Arterial Hypertension ◽  
Vascular Remodeling ◽  
Three Dimensional ◽  
Micro Computed Tomography ◽  
Differential Proteomics ◽  
Pulmonary Arterial ◽  
Adipose Dysfunction ◽  
Visceral Adipose

Pulmonary arterial hypertension (PAH) is a rare disease characterized by significant vascular remodeling. The obesity epidemic has produced great interest in the relationship between small visceral adipose tissue depots producing localized inflammatory conditions, which may link metabolism, innate immunity, and vascular remodeling. This study used novel micro computed tomography (microCT) three-dimensional modeling to investigate the degree of remodeling of the lung vasculature and differential proteomics to determine small visceral adipose dysfunction in rats with severe PAH. Sprague-Dawley rats were subjected to a subcutaneous injection of vascular endothelial growth factor receptor blocker (Sugen 5416) with subsequent hypoxia exposure for 3 weeks (SU/hyp). At 12 weeks after hypoxia, microCT analysis showed a decrease in the ratio of vascular to total tissue volume within the SU/hyp group (mean ± standard deviation: 0.27 ± 0.066; P = 0.02) with increased vascular separation (0.37 ± 0.062 mm; P = 0.02) when compared with the control (0.34 ± 0.084 and 0.30 ± 0.072 mm). Differential proteomics detected an up-regulation of complement protein 3 (C3; SU/hyp: control ratio = 2.86) and the adipose tissue–specific fatty acid binding protein-4 (FABP4, 2.66) in the heart adipose of the SU/hyp. Significant remodeling of the lung vasculature validates the efficacy of the SU/hyp rat for modeling human PAH. The upregulation of C3 and FABP4 within the heart adipose implicates small visceral adipose dysfunction. C3 has been associated with vascular stiffness, and FABP4 suppresses peroxisome proliferator–activated receptor, which is a major regulator of adipose function and known to be downregulated in PAH. These findings reveal that small visceral adipose tissue within the SU/hyp model provides mechanistic links for vascular remodeling and adipose dysfunction in the pathophysiology of PAH.

scholarly journals MicroCT analysis of vascular morphometry: a comparison of right lung lobes in the SUGEN/hypoxic rat model of pulmonary arterial hypertension

2017 ◽  
Vol 7 (2) ◽  
pp. 522-530 ◽  
Author(s):  
Erin M. Faight ◽  
Kostas Verdelis ◽  
Lee Zourelias ◽  
Rong Chong ◽  
Raymond L. Benza ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Rat Model ◽  
Vascular Remodeling ◽  
Vascular Density ◽  
Sprague Dawley ◽  
Micro Computed Tomography ◽  
Pulmonary Arterial ◽  
Lung Lobes

Pulmonary arterial hypertension (PAH) is a rare disease characterized by significant vascular remodeling within the lung. Clinical computed tomography (CT) scans are routinely used to aid in PAH diagnosis. Animal models, including the Sugen-hypoxic rat model (SU/hyp), of PAH closely mimic human PAH development. We have previously used micro-computed tomography (microCT) to find extensive right lung vascular remodeling in the SU/hyp. We hypothesized that the individual right lung lobes may not contribute equally to overall lung vascular remodeling. Sprague-Dawley rats were subjected to a subcutaneous injection of vascular endothelial growth factor receptor blocker (Sugen 5416) and subsequently exposed to chronic hypoxic conditions (10% O2) for three weeks. Following perfusion of the lung vasculature with an opaque resin (Microfil), the right lung lobes were microCT-imaged with a 10-µm voxel resolution and 3D morphometry analysis was performed separately on each lobe. As expected, we found a significantly lower ratio of vascular volume to total lobe volume in the SU/hyp compared with the control, but only in the distal lobes (inferior: 0.23 [0.21–0.30] versus 0.35 [0.27–0.43], P = 0.02; accessory: 0.27 [0.25–0.33] versus 0.37 [0.29–0.43], P = 0.06). Overall, we observed significantly fewer continuous blood vessels and reduced vascular density while having greater vascular lumen diameters in the distal lobes of both groups ( P < 0.05). In addition, the vascular separation within the SU/hyp lobes and the vascular surface area to volume ratio were significantly greater in the SU/hyp lobes compared with controls ( P < 0.03). Results for the examined parameters support the overall extensive vascular remodeling in the SU/hyp model and suggest this may be lobe-dependent.

scholarly journals Optimizing imaging of the rat pulmonary microvasculature by micro-computed tomography

2019 ◽  
Vol 9 (4) ◽  
pp. 204589401988361
Author(s):  
Yupu Deng ◽  
Katelynn J. Rowe ◽  
Ketul R. Chaudhary ◽  
Anli Yang ◽  
Shirley H.J. Mei ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Pulmonary Arterial Hypertension ◽  
High Resolution ◽  
Arterial Hypertension ◽  
Pulmonary Vascular Disease ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Pulmonary Arterial ◽  
The Impact ◽  
Lung Microcirculation

Micro-computed tomography (micro-CT) is used in pre-clinical research to generate high-resolution three-dimensional (3D) images of organs and tissues. When combined with intravascular contrast agents, micro-CT can provide 3D visualization and quantification of vascular networks in many different organs. However, the lungs present a particular challenge for contrast perfusion due to the complexity and fragile nature of the lung microcirculation. The protocol described here has been optimized to achieve consistent lung perfusion of the microvasculature to vessels < 20 microns in both normal and pulmonary arterial hypertension rats. High-resolution 3D micro-CT imaging can be used to better visualize changes in 3D architecture of the lung microcirculation in pulmonary vascular disease and to assess the impact of therapeutic strategies on microvascular structure in animal models of pulmonary arterial hypertension.

Model Characterization of Pulmonary Arterial Hypertension: Analysis of Lung Pathology with Respect to Human Disease

2020 ◽  
Author(s):  
◽  
Eptisam lambu
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Human Disease ◽  
Vascular Remodeling ◽  
Vascular Wall ◽  
Lung Pathology ◽  
Pulmonary Arterial ◽  
Lung Pathogenesis ◽  
Arterial Endothelial Cells

Pulmonary arterial hypertension (PAH) is a rare multifactorial disease characterized by abnormal high blood pressure in the pulmonary artery, or increased pulmonary vascular resistance (PVR), caused by obstruction in the small arteries of the lung. Increased PVR is also thought to be caused by abnormal vascular remodeling, due to thickening of the pulmonary vascular wall resulting from significant hypertrophy of pulmonary arterial smooth-muscle cells (PASMCs) and increased proliferation/impaired apoptosis of pulmonary arterial endothelial cells (PAECs). Herein, we investigated the mechanisms and explored molecular pathways mediating the lung pathogenesis in two PAH rat models: Monocrotaline (MCT) and Sugen5416/Hypoxia (SuHx). We analyzed these disease models to determine where the vasculature shows the most severe PAH pathology and which model best recapitulates the human disease. We investigated the role vascular remodeling, hypoxia, cell proliferation, apoptosis, DNA damage and inflammation play in the pathogenesis of PAH. Neither model recapitulated all features of the human disease, however each model presented with some of the pathology seen in PAH patients.

scholarly journals Restoration of Vitamin D Levels Improves Endothelial Function and Increases TASK-Like K+ Currents in Pulmonary Arterial Hypertension Associated with Vitamin D Deficiency

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 795
Author(s):  
Maria Callejo ◽  
Daniel Morales-Cano ◽  
Gema Mondejar-Parreño ◽  
Bianca Barreira ◽  
Sergio Esquivel-Ruiz ◽  
...  
Keyword(s):  
Vitamin D ◽  
Pulmonary Arterial Hypertension ◽  
Endothelial Function ◽  
Arterial Hypertension ◽  
Vascular Remodeling ◽  
Standard Diet ◽  
Pulmonary Vascular Remodeling ◽  
Vitamin D Levels ◽  
Pulmonary Arterial ◽  
K Currents

Background: Vitamin D (vitD) deficiency is highly prevalent in patients with pulmonary arterial hypertension (PAH). Moreover, PAH-patients with lower levels of vitD have worse prognosis. We hypothesize that recovering optimal levels of vitD in an animal model of PAH previously depleted of vitD improves the hemodynamics, the endothelial dysfunction and the ionic remodeling. Methods: Male Wistar rats were fed a vitD-free diet for five weeks and then received a single dose of Su5416 (20 mg/Kg) and were exposed to vitD-free diet and chronic hypoxia (10% O2) for three weeks to induce PAH. Following this, vitD deficient rats with PAH were housed in room air and randomly divided into two groups: (a) continued on vitD-free diet or (b) received an oral dose of 100,000 IU/Kg of vitD plus standard diet for three weeks. Hemodynamics, pulmonary vascular remodeling, pulmonary arterial contractility, and K+ currents were analyzed. Results: Recovering optimal levels of vitD improved endothelial function, measured by an increase in the endothelium-dependent vasodilator response to acetylcholine. It also increased the activity of TASK-1 potassium channels. However, vitD supplementation did not reduce pulmonary pressure and did not ameliorate pulmonary vascular remodeling and right ventricle hypertrophy. Conclusions: Altogether, these data suggest that in animals with PAH and severe deficit of vitD, restoring vitD levels to an optimal range partially improves some pathophysiological features of PAH.

scholarly journals Quantification of Arterial and Venous Morphological Markers in Pulmonary Arterial Hypertension Using Computed Tomography

CHEST Journal ◽  
2021 ◽  
Author(s):  
Farbod.N. Rahaghi ◽  
Pietro Nardelli ◽  
Eileen Harder ◽  
Inderjit Singh ◽  
Gonzalo Vegas Sanchez-Ferrero ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Morphological Markers ◽  
Pulmonary Arterial
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