Korean J Physiol Pharmacol.  2003 Apr;7(2):103-110.

Involvement of NAD (P) H Oxidase in a Potential Link between Diabetes and Vascular Smooth Muscle Cell Proliferation

• Jeong HY
• Yun MR
• Kim CD

Abstract

The cellular mechanisms that contribute to the acceleration of atherosclerosis in diabetes are poorly understood. Therefore, the potential mechanisms involved in the diabetes-dependent increase in vascular smooth muscle cell (VSMC) proliferation was investigated. Using primary culture of VSMC from streptozotocin-induced diabetic rat aorta, cell proliferation assay showed two-fold increase in cell number accompanied with enhanced superoxide generation compared to normal VSMC, 2 days after plating. Both the increased superoxide production and cell proliferation in diabetic VSMC were significantly attenuated by not only tiron (1 mM), a superoxide scavenger, but also by diphenyleneiodonium (DPI; 10micrometer), an NAD (P) H oxidase inhibitor. NAD (P) H oxidase activity in diabetic VSMC was significantly higher than that in control cell, accompanied with increased mRNA expression of p22phox, a membrane subunit of oxidase. Furthermore, inhibition of p22phox expression by transfection of antisense p22phox oligonucleotides into diabetic VSMC resulted in a decrease in superoxide production, which was accompanied by a significant inhibition of cell proliferation. Based on these results, it is suggested that diabetes-associated increase in NAD (P) H oxidase activity via enhanced expression of p22phox contributes to augmented VSMC proliferation in diabetic rats.

Keyword

Diabetes; NAD (P) H oxidase; Superoxide; VSMC proliferation

MeSH Terms

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt
Acceleration
Animals
Aorta
Atherosclerosis
Cell Count
Cell Proliferation*
Membranes
Muscle, Smooth, Vascular*
NAD*
Oligonucleotides
Oxidoreductases*
Rats
RNA, Messenger
Superoxides
Transfection
1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt
NAD
Oligonucleotides
Oxidoreductases
RNA, Messenger
Superoxides