Serotonylated fibronectin is elevated in pulmonary hypertension

Area of Science:

• Biochemistry
• Cardiovascular Research
• Pulmonary Medicine

Background:

• Serotonin (5-HT) and fibronectin (FN) are linked to pulmonary hypertension (PH).
• Previous work showed tissue transglutaminase (TGase) modifies FN into serotonylated FN (s-FN), promoting cell proliferation and migration relevant to PH.

Purpose of the Study:

• To investigate if s-FN and its binding to TGase are elevated in human and experimental PH.
• To explore the potential of s-FN as a biomarker for PH.

Main Methods:

• Fibronectin (FN) isolation, electrophoresis, immunoblotting, and densitometry.
• Analysis of serum and lung tissue samples from human PH patients and experimental animal models of PH.

Main Results:

• The ratio of serum s-FN to total FN (s-FN/FN) was significantly higher in pulmonary arterial hypertension (PAH) patients compared to controls.
• Elevated s-FN/FN levels were observed in the lungs of mice and rats with experimental PH, with increases noted even before PH development in a hypoxia model.
• Enhanced binding of TGase to FN was found in PAH patients' serum and correlated strongly with s-FN/FN levels.

Conclusions:

• Increased serotonylation of fibronectin is a characteristic feature of human and experimental pulmonary hypertension.
• Elevated s-FN levels may serve as a valuable biomarker for the diagnosis and monitoring of PH.