Protective Role of 3-Mercaptopyruvate Sulfurtransferase (MPST) in the Development of Metabolic Syndrome and Vascular Inflammation
Metabolic syndrome (MetS), a cluster of metabolic abnormalities that occur concurrently that significantly increases the risk of cardiovascular disease and mortality.  3-mercaptopyruvate sulfurtransferase (MPST), a cysteine-catabolizing enzyme that yields pyruvate and hydrogen sulfide (H2S), plays a central role in the regulation of energy homeostasis. Herein, we seek to investigate the role of MPST/H2S in MetS using a mouse model of the disease.Wilt type (WT) mice were fed a high-fat diet (HFD) for 15 weeks to induce obesity and hyperglycemia, and followed by a nitric oxide synthase inhibitor, for the additional 5 weeks to induce hypertension and MetS. This MetS mouse model caused a mild diastolic and endothelial dysfunction. We observed that, MetS was characterized by decreased levels of free H2S and sulfane-sulfur and downregulation of MPST in the aorta of animals with MetS. Global deletion of Mpst (Mpst-/-) results in increased body weight and greater glucose intolerance in mice with MetS, without affecting their blood pressure. Whole transcriptome analysis in aortic tissue revealed an upregulation of genes involved in the immune response; CD8+ cell infiltration and T-cell activation-related pathways were observed among the most affected biological processes in Mpst-/- mice with MetS. Overall design: Having established that reduced vascular MPST expression is associated with HFD+LNAME mouse model of MetS, we investigated the impact of Mpst deletion in vascular gene expression in mice with MetS. For this purpose, we performed RNAseq analysis using aortas isolated from WT and Mpst-/- mice receiving HFD+LNAME and also aortas from WT mice fed with chow diet, considered as control group.