Pulmonary hypertension and metabolic syndrome: Possible connection, PPARγ and Caveolin-1

Abstract

A number of disparate diseases can lead to pulmonary hypertension (PH), a serious disorder with a high morbidity and mortality rate. Recent studies suggest that the associated metabolic dysregulation may be an important factor adversely impacting the prognosis of PH. Furthermore, metabolic syndrome is associated with vascular diseases including PH. Inflammation plays a significant role both in PH and metabolic syndrome. Adipose tissue modulates lipid and glucose metabolism, and also produces pro- and anti-inflammatory adipokines that modulate vascular function and angiogenesis, suggesting a close functional relationship between the adipose tissue and the vasculature. Both caveolin-1, a cell membrane scaffolding protein and peroxisome proliferator-activated receptor (PPAR) γ, a ligand-activated transcription factor are abundantly expressed in the endothelial cells and adipocytes. Both caveolin-1 and PPARγ modulate proliferative and anti-apoptotic pathways, cell migration, inflammation, vascular homeostasis, and participate in lipid transport, triacylglyceride synthesis and glucose metabolism. Caveolin-1 and PPARγ regulate the production of adipokines and in turn are modulated by them. This review article summarizes the roles and inter-relationships of caveolin-1, PPARγ and adipokines in PH and metabolic syndrome.

Keywords: Adiponectin; Caveolin-1; Leptin; Metabolic Syndrome; Pulmonary hypertension; Peroxisome proliferator-activated receptor

Core tip: Pulmonary hypertension (PH) is a devastating disease with a high morbidity and mortality rate. Recent studies indicate that the metabolic alterations that occur during the course of PH have a negative effect. Importantly, PH has been observed in patients with metabolic syndrome. Caveolin-1, a membrane protein and peroxisome proliferator-activated receptor γ, a ligand activated transcription factor are abundantly expressed in vascular cells and adipocytes. They play a significant role in maintaining vascular health, and participate in glucose and lipid metabolism. Furthermore, the proximity of vasculature and adipose tissue facilitates reciprocal influence during health and disease.