The protective role of adiponectin in pulmonary vascular disease

摘要

adiponectin (APN), a 30-kDa multimeric protein exclusively produced by fat cells, reverses insulin resistance (IR) and is independently associated with a reduced risk of type 2 diabetes in apparently healthy individuals (10). However, in IR states such as obesity and type 2 diabetes, its expression and circulating levels are decreased. Low APN and high proinflammatory C-reactive protein and IL-6 levels are associated with an increased risk for IR, “metabolic syndrome,” diabetes, systemic and possibly pulmonary vascular disease (6). APN expression and secretion is downregulated by TNFα and IL-6 and upregulated by the transcription factor peroxisome proliferator-activated receptor γ (PPARγ). APN binds PDGF-BB, thereby reducing PDGF-BB bioavailability (12) and mitogenic postreceptor function in smooth muscle cells (1). Moreover, APN recently has been identified as endogenous antithrombotic factor (7), and APN overexpression significantly decreased pulmonary arterial wall thickening and right ventricular hypertrophy that develops in chronically hypoxic mice (9). Thus, APN may provide a link between insulin resistance, inflammation, thrombosis, and proliferative cardiovascular disease, e.g., pulmonary hypertension (PH) that is strongly associated with heightened PDGF-BB signaling (6).