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Quantitative analysis of hepatic macro- and microvascular alterations during cirrhogenesis in the rat

(2018) JOURNAL OF ANATOMY . 232(3). p.485-496
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Abstract
Cirrhosis represents the end-stage of any persistent chronically active liver disease. It is characterized by the complete replacement of normal liver tissue by fibrosis, regenerative nodules, and complete fibrotic vascularized septa. The resulting angioarchitectural distortion contributes to an increasing intrahepatic vascular resistance, impeding liver perfusion and leading to portal hypertension. To date, knowledge on the dynamically evolving pathological changes of the hepatic vasculature during cirrhogenesis remains limited. More specifically, detailed anatomical data on the vascular adaptations during disease development is lacking. To address this need, we studied the 3D architecture of the hepatic vasculature during induction of cirrhogenesis in a rat model. Cirrhosis was chemically induced with thioacetamide (TAA). At predefined time points, the hepatic vasculature was fixed and visualized using a combination of vascular corrosion casting and deep tissue microscopy. Three-dimensional reconstruction and data-fitting enabled cirrhogenic features to extracted at multiple scales, portraying the impact of cirrhosis on the hepatic vasculature. At the macrolevel, we noticed that regenerative nodules severely compressed pliant venous vessels from 12weeks of TAA intoxication onwards. Especially hepatic veins were highly affected by this compression, with collapsed vessel segments severely reducing perfusion capabilities. At the microlevel, we discovered zone-specific sinusoidal degeneration, with sinusoids located near the surface being more affected than those in the middle of a liver lobe. Our data shed light on and quantify the evolving angioarchitecture during cirrhogenesis. These findings may prove helpful for future targeted invasive interventions.
Keywords
3D reconstruction, cirrhosis, deep tissue microscopy, hepatic vasculature, micro-CT imaging, morphological analysis, rat liver, vascular corrosion casting, PORTAL-HYPERTENSION, LIVER-CIRRHOSIS, RAT-LIVER, SHUNTS, QUANTIFICATION, RECONSTRUCTION, ANGIOGENESIS, ARCHITECTURE, MODELS, VEIN

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Citation

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Chicago
Peeters, Geert, Charlotte Debbaut, Adrian Friebel, Pieter Cornillie, Winnok De Vos, Kasper Favere, Ingrid Vander Elst, et al. 2018. “Quantitative Analysis of Hepatic Macro- and Microvascular Alterations During Cirrhogenesis in the Rat.” Journal of Anatomy  232 (3): 485–496.
APA
Peeters, Geert, Debbaut, C., Friebel, A., Cornillie, P., De Vos, W., Favere, K., Vander Elst, I., et al. (2018). Quantitative analysis of hepatic macro- and microvascular alterations during cirrhogenesis in the rat. JOURNAL OF ANATOMY  , 232(3), 485–496.
Vancouver
1.
Peeters G, Debbaut C, Friebel A, Cornillie P, De Vos W, Favere K, et al. Quantitative analysis of hepatic macro- and microvascular alterations during cirrhogenesis in the rat. JOURNAL OF ANATOMY  . 2018;232(3):485–96.
MLA
Peeters, Geert, Charlotte Debbaut, Adrian Friebel, et al. “Quantitative Analysis of Hepatic Macro- and Microvascular Alterations During Cirrhogenesis in the Rat.” JOURNAL OF ANATOMY  232.3 (2018): 485–496. Print.
@article{8540346,
  abstract     = {Cirrhosis represents the end-stage of any persistent chronically active liver disease. It is characterized by the complete replacement of normal liver tissue by fibrosis, regenerative nodules, and complete fibrotic vascularized septa. The resulting angioarchitectural distortion contributes to an increasing intrahepatic vascular resistance, impeding liver perfusion and leading to portal hypertension. To date, knowledge on the dynamically evolving pathological changes of the hepatic vasculature during cirrhogenesis remains limited. More specifically, detailed anatomical data on the vascular adaptations during disease development is lacking. To address this need, we studied the 3D architecture of the hepatic vasculature during induction of cirrhogenesis in a rat model. Cirrhosis was chemically induced with thioacetamide (TAA). At predefined time points, the hepatic vasculature was fixed and visualized using a combination of vascular corrosion casting and deep tissue microscopy. Three-dimensional reconstruction and data-fitting enabled cirrhogenic features to extracted at multiple scales, portraying the impact of cirrhosis on the hepatic vasculature. At the macrolevel, we noticed that regenerative nodules severely compressed pliant venous vessels from 12weeks of TAA intoxication onwards. Especially hepatic veins were highly affected by this compression, with collapsed vessel segments severely reducing perfusion capabilities. At the microlevel, we discovered zone-specific sinusoidal degeneration, with sinusoids located near the surface being more affected than those in the middle of a liver lobe. Our data shed light on and quantify the evolving angioarchitecture during cirrhogenesis. These findings may prove helpful for future targeted invasive interventions.},
  author       = {Peeters, Geert and Debbaut, Charlotte and Friebel, Adrian and Cornillie, Pieter and De Vos, Winnok and Favere, Kasper and Vander Elst, Ingrid and Vandecasteele, Tim and Johann, Tim and Van Hoorebeke, Luc and Monbaliu, Diethard and Drasdo, Dirk and Hoehme, Stefan and Laleman, Wim and Segers, Patrick},
  issn         = {0021-8782},
  journal      = {JOURNAL OF ANATOMY      },
  keyword      = {3D reconstruction,cirrhosis,deep tissue microscopy,hepatic vasculature,micro-CT imaging,morphological analysis,rat liver,vascular corrosion casting,PORTAL-HYPERTENSION,LIVER-CIRRHOSIS,RAT-LIVER,SHUNTS,QUANTIFICATION,RECONSTRUCTION,ANGIOGENESIS,ARCHITECTURE,MODELS,VEIN},
  language     = {eng},
  number       = {3},
  pages        = {485--496},
  title        = {Quantitative analysis of hepatic macro- and microvascular alterations during cirrhogenesis in the~rat},
  url          = {http://dx.doi.org/10.1111/joa.12760},
  volume       = {232},
  year         = {2018},
}

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