Airway smooth muscle dysfunction in Pompe (Gaa-/-) mice.

Airway smooth muscle dysfunction in Pompe (Gaa-/-) mice. Am J Physiol Lung Cell Mol Physiol. 2017 Mar 23;:ajplung.00568.2016 Authors: Keeler AM, Liu D, Zieger M, Xiong L, Salemi J, Bellve K, Byrne BJ, Fuller DD, ZhuGe R, ElMallah MK Abstract Pompe disease is an autosomal recessive disorder caused by a deficiency of acid alpha-glucosidase (GAA) - an enzyme responsible for hydrolyzing lysosomal glycogen. Deficiency of GAA leads to systemic glycogen accumulation in the lysosomes of skeletal muscle, motor neurons and smooth muscle. Skeletal muscle and motor neuron pathology are known to contribute to respiratory insufficiency in Pompe disease, but the role of airway pathology has not been evaluated. Here we propose that GAA enzyme deficiency disrupts the function of the trachea and bronchi, and this lower airway pathology contributes to respiratory insufficiency in Pompe disease. Using an established mouse model of Pompe disease - the Gaa-/- mouse - we compared histology, pulmonary mechanics, airway smooth muscle function and calcium signaling between Gaa-/- and age matched wild type (WT) mice. Lysosomal glycogen accumulation was observed in the smooth muscle of both the bronchi and the trachea in Gaa-/- but not WT mice. Furthermore, Gaa-/- mice had hyporesponsive airway resistance and bronchial ring contraction to the bronchoconstrictive agents methacholine (Mch) and potassium chloride (KCl), and to a bronchodilator (albuterol). Finally...
Source: Am J Physiol Lung Ce... - Category: Respiratory Medicine Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research