Splanchnic-aortic inflammatory axis in experimental portal hypertension

Area of Science:

• Gastroenterology and Hepatology
• Cardiovascular Research
• Inflammation and Immunology

Background:

• Prehepatic portal hypertension is linked to low-grade splanchnic and systemic inflammation.
• Previous research indicates this condition induces liver steatosis and metabolic changes.

Purpose of the Study:

• To investigate the pathological changes in a rat model of long-term prehepatic portal hypertension.
• To explore the association between splanchnic inflammation, liver steatosis, and intestinal dysbiosis.
• To examine systemic impairments, particularly aortopathy and its relation to oxidative stress.

Main Methods:

• Utilized a rat model of long-term triple partial portal vein ligation to induce prehepatic portal hypertension.
• Assessed liver steatosis, intestinal microbiome alterations (dysbiosis, bacterial translocation), and abdominal aortic inflammation.
• Measured oxidative stress markers, including reduced nicotinamide-adenine dinucleotide phosphate [NAD(P)H] oxidase activity and reactive oxygen species.

Main Results:

• Long-term portal hypertension induced low-grade splanchnic inflammation, associated with liver steatosis and portal hypertensive intestinal vasculopathy.
• Evidence of gut dysbiosis and bacterial translocation suggests a role for the intestinal microbiome.
• Systemic effects included aortopathy, characterized by increased oxidative stress, proinflammatory cytokines, and NAD(P)H oxidase activity.

Conclusions:

• The triple partial portal vein ligation model effectively replicates chronic low-grade inflammation in prehepatic portal hypertension.
• Splanchnic inflammation, oxidative stress, and gut dysbiosis are key components of this condition.
• Findings highlight the link between portal hypertension, metabolic dysfunction, and cardiovascular pathology.