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

BACKGROUND

Hydrogen sulphide (H(2)S) 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/H(2)S pathway have been linked to various cardiovascular diseases including atherosclerosis and hypertension. An important role for H(2)S in regulating the balance between cellular growth and death has been demonstrated whereby inhibition of the endogenous CSE/H(2)S pathway results in greater apoptosis of vascular smooth muscle cells (SMCs). H(2)S 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% O(2)) 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/H(2)S pathway on SMC function. CSE-KO cells were also more susceptible to hypoxia-induced cell death, indicating a critical contribution of endogenous CSE/H(2)S pathway to the protective hypoxia stress response.

CONCLUSION

These findings support the concept that H(2)S is a crucial regulator of vascular homeostasis, the deficiency of which is associated with various pathologies, and provide further evidence that H(2)S is a potent vasculoprotectant.