TY - JOUR
T1 - Hydrogen Sulfide
T2 - A Therapeutic Option in Systemic Sclerosis
AU - Abdulle, Amaal Eman
AU - van Goor, Harry
AU - Mulder, Douwe J.
PY - 2018/12
Y1 - 2018/12
N2 - Systemic sclerosis (SSc) is a lethal disease that is characterized by auto-immunity, vascular injury, and progressive fibrosis of multiple organ systems. Despite the fact that the exact etiology of SSc remains unknown, oxidative stress has been associated with a large range of SSc-related complications. In addition to the well-known detrimental properties of reactive oxygen species (ROS), gasotransmitters (e.g., nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S)) are also thought to play an important role in SSc. Accordingly, the diverse physiologic actions of NO and CO and their role in SSc have been previously studied. Recently, multiple studies have also shown the importance of the third gasotransmitter H2S in both vascular physiology and pathophysiology. Interestingly, homocysteine (which is converted into H2S through the transsulfuration pathway) is often found to be elevated in SSc patients; suggesting defects in the transsulfuration pathway. Hydrogen sulfide, which is known to have several effects, including a strong antioxidant and vasodilator effect, could potentially play a prominent role in the initiation and progression of vasculopathy. A better understanding of the actions of gasotransmitters, like H2S, in the development of SSc-related vasculopathy, could help to create early interventions to attenuate the disease course. This paper will review the role of H2S in vascular (patho-)physiology and potential disturbances in SSc. Moreover, current data from experimental animal studies will be reviewed. Lastly, we will evaluate potential interventional strategies.
AB - Systemic sclerosis (SSc) is a lethal disease that is characterized by auto-immunity, vascular injury, and progressive fibrosis of multiple organ systems. Despite the fact that the exact etiology of SSc remains unknown, oxidative stress has been associated with a large range of SSc-related complications. In addition to the well-known detrimental properties of reactive oxygen species (ROS), gasotransmitters (e.g., nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S)) are also thought to play an important role in SSc. Accordingly, the diverse physiologic actions of NO and CO and their role in SSc have been previously studied. Recently, multiple studies have also shown the importance of the third gasotransmitter H2S in both vascular physiology and pathophysiology. Interestingly, homocysteine (which is converted into H2S through the transsulfuration pathway) is often found to be elevated in SSc patients; suggesting defects in the transsulfuration pathway. Hydrogen sulfide, which is known to have several effects, including a strong antioxidant and vasodilator effect, could potentially play a prominent role in the initiation and progression of vasculopathy. A better understanding of the actions of gasotransmitters, like H2S, in the development of SSc-related vasculopathy, could help to create early interventions to attenuate the disease course. This paper will review the role of H2S in vascular (patho-)physiology and potential disturbances in SSc. Moreover, current data from experimental animal studies will be reviewed. Lastly, we will evaluate potential interventional strategies.
KW - gasotransmitters
KW - systemic sclerosis
KW - vasculopathy
KW - endothelial injury
KW - therapeutic intervention
KW - CYSTATHIONINE-GAMMA-LYASE
KW - NITRIC-OXIDE SYNTHASE
KW - NAILFOLD VIDEOCAPILLAROSCOPIC PATTERNS
KW - MICROVASCULAR ENDOTHELIAL-CELLS
KW - ANIMATION-LIKE STATE
KW - CARBON-MONOXIDE
KW - HEME OXYGENASE-1
KW - SODIUM THIOSULFATE
KW - OXIDATIVE DAMAGE
KW - BLOOD-PRESSURE
U2 - 10.3390/ijms19124121
DO - 10.3390/ijms19124121
M3 - Review article
VL - 19
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1422-0067
IS - 12
M1 - 4121
ER -