Developmental alveologenesis: new roles for ApoE and LDL receptor

Pulmonary developmental alveologenesis occurs, in substantial part, by subdivision (septation) of the gas-exchange saccules of the morphologically immature lung. It determines the starting point of age- and disease-related alveolar loss. Because alveologenesis requires additional cell membranes, we previously asked whether apoE-/-, which delivers lipids to cells, affects pulmonary alveologenesis; male apoE-/- mice had impaired alveologenesis. We now report that, in contrast to male apoE-/- mice, female apoE mice had full developmental alveologenesis. Among mice null for LDL receptor (Ldlr-/-), the receptor for apoE-/-, females had full alveologenesis; by contrast, Ldlr-/- males, as previously shown for apoE males, had impaired alveologenesis. Thus, the absence of apoE and its receptor, Ldlr, results in impaired developmental alveologenesis in males, but their absence does not impair architectural developmental alveologenesis in females. We conclude 1) regulation of alveologenesis is a new function for apoE and Ldlr, 2) one expressed in a sexually dimorphic manner, and 3) females have different molecular requirements for alveologenesis than males, which protects them from its impairment by the absence of apoE and its receptor.