Oxidative stress in asthma pathogenesis: mechanistic insights and implications for airway smooth muscle dysfunction.

Abstract

Airway smooth muscle (ASM) dysfunction is a key factor in the narrowing of airways in asthma patients, characterized by excessive secretion of inflammatory factors, increased mass, and amplified contractile responses. These pathological features are instrumental in the propagation of airway inflammation, structural remodeling, and the escalation of airway hyperresponsiveness (AHR), which are also principal factors underlying the limitations of current therapeutic strategies. In asthmatic ASM, an imbalance between oxidant production and antioxidant defenses culminates in oxidative stress, which is involved in the excessive secretion of inflammatory factors, increased mass, and amplified contractile responses of ASM, and is a critical etiological factor implicated in the dysregulation of ASM function. The molecular pathways through which oxidative stress exerts its effects on ASM in asthma are multifaceted, with the Nrf2/HO-1, MAPK, and PI3K/Akt pathways being particularly noteworthy. These characteristic pathways play a potential role by connecting with different upstream and downstream signaling molecules and are involved in the amplification of ASM inflammatory responses, increased mass, and AHR. This review provides a comprehensive synthesis of the phenotypic expression of ASM dysfunction in asthma, the interplay between oxidants and antioxidants, and the evidence base and molecular underpinnings linking oxidative stress to ASM dysfunction. Given the profound implications of ASM dysfunction on the airflow limitation in asthma and the seminal role of oxidative stress in this process, a deeper exploration of these mechanisms is essential for unraveling the pathogenesis of asthma and may offer novel perspectives for its prophylaxis and management.