Fat, fire and muscle--the role of adiponectin in pulmonary vascular inflammation and remodeling.

Pulmonary hypertension is a life-threatening condition that results from a heterogeneous group of diseases, many of which demonstrate characteristic pathologic changes of pulmonary vascular inflammation and remodeling. Recent clinical studies indicate obesity to be a risk factor for the development of pulmonary hypertension; however, the mechanisms leading to this association are unknown. Adipocytes secrete multiple bioactive mediators that can influence inflammation and tissue remodeling, suggesting that adipose tissue may directly influence the pathogenesis of pulmonary hypertension. One of these mediators is adiponectin, a protein with a wide range of metabolic, anti-inflammatory, and anti-proliferative activities. Paradoxically, adiponectin is present in high concentration in the serum of lean healthy individuals, but decreases in obesity. Studies suggest that relative adiponectin-deficiency may contribute to the development of inflammatory diseases in obesity, and recent animal studies implicate adiponectin in the pathogenesis of pulmonary hypertension. Most notably, experimental studies show that adiponectin can reduce lung vascular remodeling in response to inflammation and hypoxia. Moreover, mice deficient in adiponectin develop a spontaneous lung vascular phenotype characterized by age-dependent increases in peri-vascular inflammatory cells and elevated pulmonary artery pressures. Emerging evidence indicates adiponectin's effects are mediated through anti-inflammatory and anti-proliferative actions on cells in the lung. This review aims to synthesize the existing data related to adiponectin's effects on the pulmonary vasculature and to discuss how changes in adiponectin levels might contribute to the development of pulmonary hypertension.