1: Exp Biol Med (Maywood). 2003 May;228(5):572-5. 

Antiapoptotic action of carbon monoxide on cultured vascular smooth muscle
cells.

Liu XM, Chapman GB, Peyton KJ, Schafer AI, Durante W.

Houston VA Medical Center and the Departments of Medicine and Pharmacology,
Baylor College of Medicine, Houston, Texas 77030, USA.

Vascular smooth muscle cells (SMCs) generate carbon monoxide (CO) from the
degradation of heme by the enzyme heme oxygenase. Because recent studies
indicate that CO influences the properties of vascular SMCs, we examined whether
this diatomic gas regulates apoptosis in vascular SMCs. Treatment of cultured
rat aortic SMCs with a cytokine cocktail consisting of interleukin-1beta (5
ng/ml), tumor necrosis factor-alpha (20 ng/ml), and interferon-gamma (200 U/ml)
for 48 hr stimulated apoptosis, as demonstrated by DNA laddering, caspase-3
activation, and annexin V staining. However, the exogenous addition of CO (200
ppm) completely blocked cytokine-mediated apoptosis. The antiapoptotic action of
CO was partially reversed by the soluble guanylate cyclase inhibitor,
H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 microM). In contrast, the p38
mitogen-activated protein kinase inhibitor, SB203580 (10 microM), had no effect
on SMC apoptosis. These findings indicate that CO is a potent inhibitor of
vascular SMC apoptosis and that it blocks apoptosis, in part, by activating the
cGMP signaling pathway. The ability of CO to inhibit vascular SMC apoptosis may
play a critical role in attenuating lesion formation at sites of arterial
damage.

PMID: 12709589 [PubMed - indexed for MEDLINE]