Abstract
Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function, and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese mice expressed higher levels of leukocyte adhesion markers and lower levels of cell-cell junctional proteins when compared to lean mice. We tested whether systemic factors are responsible for these alterations in the pulmonary endothelium; treatment of primary lung endothelial cells with obese serum enhanced the expression of adhesion proteins and reduced the expression of endothelial junctional proteins when compared to lean serum. Alterations in pulmonary endothelial cells observed in obese mice were associated with enhanced susceptibility to LPS-induced lung injury. Restoring serum adiponectin levels reversed the effects of obesity on the lung endothelium and attenuated susceptibility to acute injury. Our work indicates that obesity impairs pulmonary vascular homeostasis and enhances susceptibility to acute injury and provides mechanistic insight into the increased prevalence of ARDS in obese humans.
Highlights
Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown
While little is known about the effects of obesity on pulmonary vascular homeostasis, studies using adiponectin-deficient mice provide insight into the interaction between adipose tissue and the pulmonary circulation[15,16]
While adiponectin deficient mice do not reflect the complex physiology of obesity, the above studies provoked our central hypothesis, namely that obesity disrupts pulmonary vascular homeostasis thereby contributing to the onset of inflammatory vascular diseases in the lung
Summary
Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. The mechanisms by which obesity impairs vascular tissue functions are complex and not fully elucidated it is generally accepted that chronic low-grade systemic inflammation plays a role in promoting disease[3]. While clinical studies have yet to establish whether the prevalence of pulmonary vascular diseases such as pulmonary arterial hypertension are increased in obese individuals, emerging evidence suggests that obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS)[10,11,12]. While little is known about the effects of obesity on pulmonary vascular homeostasis, studies using adiponectin-deficient mice provide insight into the interaction between adipose tissue and the pulmonary circulation[15,16]. We tested this hypothesis in mouse models of diet-induced obesity and studied the mechanisms underlying the observed effects of obesity on pulmonary injury
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