Cystathionine gamma-lyase-deficient smooth muscle cells exhibit redox imbalance and apoptosis under hypoxic stress conditions

BACKGROUND:

Hydrogen sulphide (H₂S) has recently emerged as a novel and important gasotransmitter in the cardiovascular system, where it is generated mainly by cystathionine gamma-lyase (CSE). Abnormal metabolism and functions of the CSE/H₂S pathway have been linked to various cardiovascular diseases including atherosclerosis and hypertension. An important role for H₂S in regulating the balance between cellular growth and death has been demonstrated whereby inhibition of the endogenous CSE/H₂S pathway results in greater apoptosis of vascular smooth muscle cells (SMCs). H₂S is increasingly recognized as a critical regulator of vascular integrity, but its role in SMCs during hypoxia has not been explored in a model of CSE deficiency.

METHODS:

Cell viability, apoptosis, redox status and mitochondrial activity in hypoxia-exposed (12 h at 1% O₂) SMCs derived from the mesenteric artery of CSE-knockout (CSE-KO) mice were analyzed. These were compared with those from CSE-wild-type (CSE-WT) mice.

RESULTS:

CSE-KO cells exhibited redox imbalance and aberrant mitochondrial activity versus CSE-WT cells, indicating an essential regulatory role for the endogenous CSE/H₂S pathway on SMC function. CSE-KO cells were also more susceptible to hypoxia-induced cell death, indicating a critical contribution of endogenous CSE/H₂S pathway to the protective hypoxia stress response.

CONCLUSION:

These findings support the concept that H₂S is a crucial regulator of vascular homeostasis, the deficiency of which is associated with various pathologies, and provide further evidence that H₂S is a potent vasculoprotectant.