Identification of LTBP-2 as a plasma biomarker for right ventricular dysfunction in human pulmonary arterial hypertension.

Although right ventricular (RV) function is the primary determinant of morbidity and mortality in pulmonary arterial hypertension (PAH), the molecular mechanisms of RV remodeling and the circulating factors reflecting its function remain largely elusive. In this context, the identification of new molecular players implicated in maladaptive RV remodeling along with the optimization of risk stratification approaches in PAH are key priorities. Through combination of transcriptomic and proteomic profiling of RV tissues with plasma proteome profiling, we identified a panel of proteins, mainly related to cardiac fibrosis, similarly upregulated in the RV and plasma of patients with PAH with decompensated RV.

Amino acids are sensitive glucagon receptor-specific biomarkers for glucagon-like peptide-1 receptor/glucagon receptor dual agonists.

Aim: The aim of this study was to evaluate amino acids as glucagon receptor (GCGR)-specific biomarkers in rodents and cynomolgus monkeys in the presence of agonism of both glucagon-like peptide-1 receptor (GLP1R) and GCGR with a variety of dual agonist compounds.

Materials And Methods: Primary hepatocytes, rodents (normal, diet-induced obese and GLP1R knockout) and cynomolgus monkeys were treated with insulin (hepatocytes only), glucagon (hepatocytes and cynomolgus monkeys), the GLP1R agonist, dulaglutide, or a variety of dual agonists with varying GCGR potencies.

Results: A long-acting dual agonist, Compound 2, significantly decreased amino acids in both wild-type and GLP1R knockout mice in the absence of changes in food intake, body weight, glucose or insulin, and increased expression of hepatic amino acid transporters.