Plasma free H2S levels are elevated in patients with cardiovascular disease

Elvis A Peter, Xinggui Shen, Shivang H Shah, Sibile Pardue, John D Glawe, Wayne W Zhang, Pratap Reddy, Nuri I Akkus, Jai Varma, Christopher G Kevil, Elvis A Peter, Xinggui Shen, Shivang H Shah, Sibile Pardue, John D Glawe, Wayne W Zhang, Pratap Reddy, Nuri I Akkus, Jai Varma, Christopher G Kevil

Abstract

Background: Hydrogen sulfide (H2S) has been implicated in regulating cardiovascular pathophysiology in experimental models. However, there is a paucity of information regarding the levels of H2S in health and cardiovascular disease. In this study we examine the levels of H2S in patients with cardiovascular disease as well as bioavailability of nitric oxide and inflammatory indicators.

Methods and results: Patients over the age of 40 undergoing coronary or peripheral angiography were enrolled in the study. Ankle brachial index (ABI) measurement, measurement of plasma-free H2S and total nitric oxide (NO), thrombospondin-1 (TSP-1), Interleukin-6 (IL-6), and soluble intercellular adhesion molecule-1 (sICAM-1) levels were performed. Patients with either coronary artery disease alone (n = 66), peripheral arterial disease (PAD) alone (n = 13), or any vascular disease (n = 140) had higher plasma-free H2S levels compared to patients without vascular disease (n = 53). Plasma-free H2S did not distinguish between disease in different vascular beds; however, total NO levels were significantly reduced in PAD patients and the ratio of plasma free H2S to NO was significantly greater in patients with PAD. Lastly, plasma IL-6, ICAM-1, and TSP-1 levels did not correlate with H2S or NO bioavailability in either vascular disease condition.

Conclusions: Findings reported in this study reveal that plasma-free H2S levels are significantly elevated in vascular disease and identify a novel inverse relationship with NO bioavailability in patients with peripheral arterial disease.

Trial registration: ClinicalTrials.gov NCT01407172.

Keywords: coronary artery disease; hydrogen sulfide; nitric oxide; peripheral arterial disease.

Figures

Figure 1.
Figure 1.
Study organization flow chart. A total of 193 patients were used for analysis, including a total of 74 PAD patients along with 119 non‐PAD patients who were subsequently diagnosed with or without CAD after cardiac catheterization. CAD indicates coronary artery disease; PAD, peripheral artery disease.
Figure 2.
Figure 2.
Effect of blood collection tubes on plasma hydrogen sulfide (H2S) levels. Venous blood was collected from healthy volunteers in either lithium heparin or ethylenediaminetetraacetic acid (EDTA) vacutainer collection tubes. A, reports the differences in plasma free H2S between the different collection tubes vs lysed red blood cells (RBC) (**P<0.01 vs lithium heparin collection tubes). B, illustrates amount of cell free hemoglobin measured using the Drabkin assayin plasma from blood collected in various tubes vs lysed red blood cells (**P<0.01 vs lithium heparin collection tubes).
Figure 3.
Figure 3.
Plasma‐free hydrogen sulfide to total NO ratio by vascular disease. The ratio of plasma‐free hydrogen sulfide to total NO was calculated per vascular disease cohort. Free H2S:NOx ratio was significantly elevated in patients with PAD alone over all other comparison cohorts, *P<0.05. No vascular disease n=53, CAD alone n=66, PAD alone n=13, and any vascular disease n=140. CAD indicates coronary artery disease; H2S, hydrogen sulfide; NO, nitric oxide; PAD, peripheral artery disease.

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