Superoxide mediates the medial smooth muscle cell apoptosis associated with vascular injury

• Published in: The FASEB journal 2006-03, Vol.20 (5), p.A1453-A1453
• Main Authors: Dammanahalli, Jagadeesha Karigowda, DeLeon, Jason, Miller, Francis J, Bhalla, Ramesh C
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.20.5.A1453-c

Cellular events within the medial layer contribute to neointima formation following vascular injury. However, the role of reactive oxygen species, and the effect of antioxidant therapy, on medial smooth muscle cell (SMC) apoptosis early following vascular injury is not known. We assessed whether reduction of superoxide levels by tempol (1 mM in drinking water) will effect the duration and magnitude of medial SMC apoptosis at early (1–3 d), mid (7 d) and late (14d) time points following balloon‐injury of rat carotid artery. Balloon injury increased superoxide production, medial SMC apoptosis index, Bax positive medial SMC index, expression of Bax/Bcl‐xL ratio, and caspase ‐3 expression, as compared to uninjured arteries during the early time point (1–3 d). Tempol attenuated medial SMC apoptosis, mitochondrial apoptotic signaling pathway of Bcl‐2 family proteins and increased medial SMC density during the early time points (1–3 d) following balloon injury. Inhibition of medial SMC apoptosis by tempol was maximal at the early time points and persisted throughout neointima formation. The effect of tempol on medial SMC apoptosis was associated with a significant (46%) reduction in neointima formation by day 14. These findings suggest that inhibition of medial SMC apoptosis during the early phase following vascular injury may be important in modifying the kinetics of neointima formation. (Supported by AHA and NIH 14388 and HL081750).