Does inflammation trigger fibrosis in hypertrophic cardiomyopathy: a burning question?

Asthma is characterized by chronic airway inflammation and remodeling that can be (partially) suppressed by inhaled corticosteroids (ICS). Plasminogen activator inhibitor-1, encoded by the SERPINE1 gene, is the key inhibitor of the plasminogen activator system that affects tissue repair and remodeling. We studied associations between a functional SERPINE1 -675 4G/5G promoter polymorphism and asthma development and severity and response to ICS. Longitudinal cohorts of 281 asthmatics and their non-asthmatic spouses and the general population (n=1390) were studied. No significant associations were found with asthma development and IgE levels, nor with FEV1 in non-asthmatic controls. Asthmatic subjects carrying the SERPINE1 5G allele had higher IgE and lower lung function levels at follow-up, lower maximally attained lung function level, and faster lung function decline compared to individuals with the 4G/4G genotype. ICS treatment showed an immediate improvement in FEV1 level in asthmatics carrying the 5G allele. However, these asthmatics still had the fastest rate of FEV1 decline after initiating ICS treatment. Finally, the 5G allele was associated with a lower prevalence of complete asthma remission at follow-up. These findings suggest that SERPINE1 is not an asthma susceptibility gene, but rather affects the severity, progression and long-term ICS response in asthma.