COPD: Heme Oxygenase-1 Shows Promise

Recent studies of heme oxygenase-1 (HO-1) show that it may have therapeutic uses in cases of chronic inflammation, such as COPD, according to a review of published literature on the topic. The review was conducted by Stefan W. Ryter, PhD, and Augustine M.K. Choi, MD, of Joan and Sanford I. Weill Department of Medicine, at New York-Presbyterian Hospital, Weill Cornell Medical College, and was published in Translational Research, the Journal of Laboratory and Clinical Medicine in January, 2016.

The researchers begin by saying that HO-1 “remains an attractive therapeutic target for the treatment of inflammatory conditions” and that it “may function as a pleiotropic regulator of inflammatory signaling programs through the generation of its biologically active end products,” specifically carbon monoxide (CO) and biliverdin-IXa (BV), which is converted into bilirubin-IXa(BR). The areas of treatment that the reviewers included are lung and vascular injury, sepsis, ischemia-reperfusion injury, and transplant rejection.

Microsatellite dinucleotide (GT)n length polymorphisms on the gene HMOX1, which is located on chromosome 22q13.1, may “result in the impaired transcriptional regulation and decreased expression of HO-1 in individuals that carry the long (L) allele of this polymorphism,” say the researchers. Several diseases, including cardiovascular disease and chronic kidney disease, are associated with the HMOX1 promoter polymorphisms.

“Additional studies reported associations of the long allele of (GT)n with chronic obstructive pulmonary disease,” among other respiratory conditions, report the researchers One recent study found that there was “no association between 5 SNPs and HMOX1 gene expression or lung functional decline in patients with COPD” leading the reviewers to conclude, “association studies, when positive, have suggested that a genetically dependent downregulation of HO-1 expression may arise in subpopulations possibly linked to increased susceptibility to oxidative stress, inflammation, and associated diseases” though they caution that such a hypothesis is inconclusive and more research is necessary.

The review covers several other studies which investigated the possible therapeutic uses of HO-1 for conditions other than COPD. The reviewers conclude suggest, “the putative role of HO-1 in the modulation of the adaptive immune response represents an area of active investigation.”