Phosphodiesterases in the Liver as Potential Therapeutic Targets of Cirrhotic Portal Hypertension

Autor: Denise Schaffner, Irmgard Merfort, Jonel Trebicka, Peter Deibert, Wolfgang Kreisel, Adhara Lazaro, Annette Schmitt-Graeff
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Cirrhosis
sGC
Metabolite
Review
Pharmacology
lcsh:Chemistry
chemistry.chemical_compound
0302 clinical medicine
Molecular Targeted Therapy
lcsh:QH301-705.5
Cyclic GMP
Spectroscopy
PDE-5
Phosphodiesterase
portal hypertension
General Medicine
Pathophysiology
Computer Science Applications
PDE-5 inhibitors
Portal hypertension
030211 gastroenterology & hepatology
Signal Transduction
NO-cGMP pathway
liver cirrhosis
sGC modulators
Catalysis
Nitric oxide
Inorganic Chemistry
03 medical and health sciences
nitric oxide
Hypertension
Portal
Guanosine monophosphate
medicine
Humans
Physical and Theoretical Chemistry
Molecular Biology
Cyclic Nucleotide Phosphodiesterases
Type 5
business.industry
Organic Chemistry
medicine.disease
cGMP
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
chemistry
Guanylate Cyclase
hepatic zonation
Liver function
business
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 21, Iss 6223, p 6223 (2020)
ISSN: 1422-0067
Popis: Liver cirrhosis is a frequent condition with high impact on patients’ life expectancy and health care systems. Cirrhotic portal hypertension (PH) gradually develops with deteriorating liver function and can lead to life-threatening complications. Other than an increase in intrahepatic flow resistance due to morphological remodeling of the organ, a functional dysregulation of the sinusoids, the smallest functional units of liver vasculature, plays a pivotal role. Vascular tone is primarily regulated by the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, wherein soluble guanylate cyclase (sGC) and phosphodiesterase-5 (PDE-5) are key enzymes. Recent data showed characteristic alterations in the expression of these regulatory enzymes or metabolite levels in liver cirrhosis. Additionally, a disturbed zonation of the components of this pathway along the sinusoids was detected. This review describes current knowledge of the pathophysiology of PH with focus on the enzymes regulating cGMP availability, i.e., sGC and PDE-5. The results have primarily been obtained in animal models of liver cirrhosis. However, clinical and histochemical data suggest that the new biochemical model we propose can be applied to human liver cirrhosis. The role of PDE-5 as potential target for medical therapy of PH is discussed.
Databáze: OpenAIRE
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