Chronic Obstructive Pulmonary Disease

Biography

Biography: Yong Xiao Wang

Abstract

COPD is the third leading cause of mortality in the world and will be the second leading cause of death by 2020. However, the molecular mechanisms for this devastating disease remain largely unknown; currently, the clinical therapeutic options are neither specific and nor always effective. A major characteristic of COPD is expiratory airflow limitation, which can be attributed to airway hyperresponsiveness. A very important player (VIP) in airway hyperresponsiveness is the increased contraction of airway smooth muscle cells (ASMCs). An increase in intracellular calcium ([Ca²⁺]_i) is a key factor in the increased contraction in AMCs. Consistent with this view, bronchodilators including muscarinic receptor antagonists, β-adrenergic receptor agonists and corticosteroids are used as the first-line drugs in the clinical treatment of COPD, and the functional role of all these forefront drugs are associated with their inhibition of the increased [Ca²⁺]_i and contraction in ASMCs. Multiple ion channels such as inositol trisphosphate receptor (IP₃R)/Ca²⁺ release channel, ryanodine receptor (RyR)/Ca²⁺ release channel and canonical transient receptor potential-3 (TRPC3) channel, play a major role in initiation and maintenance of [Ca²⁺]_i. Recent studies suggest that these channels are essential for airway hyperresponsiveness in COPD and other pulmonary diseases. Equally interestingly, IP₃R, RyR and TRPC3 channels are highly sensitive to reactive oxygen species (ROS), and ROS are well known to mediate airway hyperresponsiveness and other unleashed cellular responses in COPD. ROS are primarily produced by mitochondria and NADPH oxidase (NOX). A number of antioxidants targeted at mitochondria and/or NOX are currently used in clinical trials and show potential effectiveness in the treatment of COPD. ROS may implement their role in COPD by causing of oxidation of IP₃R, RyR and TRPC3 channels, leading to their hyperfunctions. Thus, it is reasonably believed that genetic and pharmacological inhibition of these channels, like antioxidants, may also be effective for therapies of COPD. In support, studies using animals have revealed their therapeutic for airway hyperresponsiveness and COPD.