Scavenger Receptor B1 involvement in COPD pathogenesis

Abstract

Chronic obstructive pulmonary disease (COPD) is one of the main causes of morbidity and mortality in the United States. In 2020, almost 150,000 people died from COPD, making it the sixth leading cause of death and the fifth disease-related cause of death, behind heart disease, cancer, COVID-19, accidents, and stroke. Although exposure to cigarette smoke has been shown to be the main risk factor for COPD, the mechanisms underlying this association remain unclear as many smokers do not develop COPD. Several mechanisms contribute to the pathogenesis of COPD, such as pulmonary influx of inflammatory cells, imbalance between proteolytic and antiproteolytic molecules, alteration of the redox homeostasis. Among them, oxidative stress has been suggested to be the major driving mechanism in COPD pathogenesis. There is increased oxidative stress in the lungs of COPD patients due to exogenous oxidants in cigarette smoke and as a consequence of endogenous generation of reactive oxygen species by inflammatory cells and the consequent decrease in antioxidants content. The scavenger receptor BI (SRB1), beside playing a key role in mediating the uptake of high-density lipoprotein (HDL)-derived cholesterol and cholesteryl ester in tissues, it is also involved in the tissue antioxidant uptake for tocopherol. Loss of SRB1 significantly decreases tocopherol lung content making lung tissue more susceptible to oxidative damage. Therefore, because of its role in modulating the antioxidant defense in lung tissues, the loss of SRB1 may contribute to the development of COPD by preventing the tissue uptake of antioxidants molecules such as tocopherol.