Grant: Operating Grant

Airway muscle from asthmatics and from animal models of asthma exhibits increased rate and extent of shortening as well as increased force generation. Many hypotheses on the mechanisms responsible for this enhanced contractility have been formulated but have never been tested thoroughly. Our data from human bronchial biopsies indicate that the gene expression of certain contractile proteins is altered in asthmatics compared to normal subjects. These proteins are responsible for the movement and force generating capacity of muscle as well as its activation. It is therefore conceivable that the altered expression of these proteins directly enhances airway muscle contractility in asthma. Thus, we propose to use state of the art technology and combine mechanics measurements directly at the molecular, muscle strip, and whole animal levels to elucidate the causes of airway muscle abnormality in asthma. Understanding the fundamental abnormality of airway muscle in experimental models of asthma will help formulate strategies to alleviate asthma.