Document Type


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School of Medicine


Cardiovascular and Thoracic Surgery


Hydrogen sulfide (H2S) has emerged as an important physiological and pathophysiological signaling molecule in the cardiovascular system influencing vascular tone, cytoprotective responses, redox reactions, vascular adap- tation, and mitochondrial respiration. However, bioavailable levels of H2S in its various biochemical metabolite forms during clinical cardiovascular disease remain poorly understood. We performed a case-controlled study to quantify and compare the bioavailability of various biochemical forms of H2S in patients with and without cardiovascular disease (CVD). In our study, we used the reverse-phase high performance liquid chromatography monobromobimane assay to analytically measure bioavailable pools of H2S. Single nucleotide polymorphisms (SNPs) were also identified using DNA Pyrosequencing. We found that plasma acid labile sulfide levels were significantly reduced in Caucasian females with CVD compared with those without the disease. Conversely, plasma bound sulfane sulfur levels were significantly reduced in Caucasian males with CVD compared with those without the disease. Surprisingly, gender differences of H2S bioavailability were not observed in African Americans, although H2S bioavailability was significantly lower overall in this ethnic group compared to Caucasians. We also performed SNP analysis of H2S synthesizing enzymes and found a significant increase in cystathionine gamma-lyase (CTH) 1364 G-T allele frequency in patients with CVD compared to controls. Lastly, plasma H2S bioavailability was found to be predictive for cardiovascular disease in Caucasian subjects as de- termined by receiver operator characteristic analysis. These findings reveal that plasma H2S bioavailability could be considered a biomarker for CVD in an ethnic and gender manner. Cystathionine gamma-lyase 1346 G-T SNP might also contribute to the risk of cardiovascular disease development.

Source Citation

Rajpal, S., Katikaneni, P., Deshotels, M., Pardue, S., Glawe, J., Shen, X., Akkus, N., Modi, K., Bhandari, R., Dominic, P., Reddy, P., Kolluru, G. K., & Kevil, C. G. (2018). Total sulfane sulfur bioavailability reflects ethnic and gender disparities in cardiovascular disease. Redox Biology, 15, 480–489.


Received 26 November 2017; Received in revised form 4 January 2018; Accepted 11 January 2018

Available online 03 February 2018 2213-2317/ © 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (



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