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Updated: Jul 18, 2026
Murine Aortic Crush Injury: An Efficient In Vivo Model of Smooth Muscle Cell Proliferation and Endothelial Function
Published on: June 11, 2017
Impaired extracellular matrix degradation in aortic vessels of cirrhotic rats
Guillermo Fernández-Varo1, Manuel Morales-Ruiz, Josefa Ros
1Department of Biochemistry and Molecular Genetics, Hospital Clínic Universitari, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Background/Aims:
Thinning of the vascular wall occurs in conductance vessels of cirrhotic rats. Increased nitric oxide synthase (NOS) activity has been involved in the pathogenesis of this phenomenon. Therefore, we assessed the NO-regulated cell signaling pathways participating in vascular remodeling in cirrhosis.
Methods:
Aortas were obtained from 15 control and 15 cirrhotic rats. Phosphorylated p38 MAPK and ERK1/2 were used to evaluate the activation of cell MAPK signaling pathways. Extracellular matrix (ECM) turnover was estimated by measuring matrix metalloproteinases (MMPs) activity and protein expression of collagen IV, MMP-2, MMP-9 and tissue inhibitor of MMPs (TIMP)-2. Thereafter, 12 control and 12 cirrhotic rats received Nomega-nitro-L-arginine-methyl-ester or vehicle daily for 11 weeks.
Results:
Cirrhotic vessels showed a reduction in ERK1/2 phosphorylation, lower MMP activity, decreased MMPs expression and higher collagen IV and TIMP-2 abundance, compared to control rats. Chronic NOS inhibition normalized ERK1/2 phosphorylation and MMPs activity, increased MMPs abundance and decreased TIMP-2 expression in cirrhotic rats.
Conclusions:
Vascular remodeling in cirrhotic rats is mediated by down-regulation of cell growth and impaired ERK1/2 activation and subsequent imbalance of ECM turnover. These results further stress the importance of vascular NO overactivity in the reduction of vascular wall thickness in cirrhosis.
Insights
Vascular remodeling in cirrhosis involves reduced ERK1/2 activation and extracellular matrix imbalance. Inhibiting nitric oxide synthase (NOS) normalized these pathways, highlighting NO
Area of Science:
- Vascular biology
- Cell signaling
- Liver disease research
Background:
- Cirrhosis leads to vascular wall thinning in major arteries.
- Increased nitric oxide synthase (NOS) activity is implicated in this vascular remodeling.
- Understanding NO-regulated pathways is crucial for cirrhosis research.
Purpose of the Study:
- To investigate NO-regulated cell signaling pathways involved in vascular remodeling in cirrhotic rats.
- To assess the role of mitogen-activated protein kinase (MAPK) pathways, specifically ERK1/2 and p38.
- To evaluate the impact on extracellular matrix (ECM) turnover, including matrix metalloproteinases (MMPs) and their inhibitors.
Main Methods:
- Aorta analysis from control and cirrhotic rats.
- Measurement of phosphorylated p38 MAPK and ERK1/2 to assess pathway activation.
- Quantification of MMP activity, MMPs and TIMP-2 expression, and collagen IV levels.
- In vivo study involving chronic NOS inhibition with Nomega-nitro-L-arginine-methyl-ester.
Main Results:
- Cirrhotic rat aortas exhibited reduced ERK1/2 phosphorylation, lower MMP activity and expression, and increased collagen IV and TIMP-2.
- Chronic NOS inhibition in cirrhotic rats restored ERK1/2 phosphorylation and MMP activity.
- NOS inhibition also increased MMP expression and decreased TIMP-2 levels in cirrhotic rat aortas.
Conclusions:
- Vascular remodeling in cirrhosis is characterized by impaired ERK1/2 activation and ECM turnover imbalance.
- Vascular nitric oxide (NO) overactivity plays a significant role in reducing vascular wall thickness in cirrhosis.
- Targeting NO pathways may offer therapeutic strategies for vascular complications in liver disease.
