Korean J Thorac Cardiovasc Surg.  1999 Apr;32(4):333-340.

The Effects of Glucose , Insulin and Angiotensin II on Plasminogen Activator Inhibitor-1 Expression and Growth of Aortic Vascular Smooth Muscle Cell in Rats

• Choi SY
• Lee IG
• Han SS
• Kim JH
• Park CK
• Lee KS
• Yoo YS
• Kim GS
• Kim YN
• Kim KB

Abstract

BACKGROUND: Plasminogen activator inhibitor-1(PAI-1) is known as the primary physiological inhibitor of tissue-type plasminogen activator(t-PA) in the plasma, and is present within the atherosclerotic vessels. Increased plasma levels of PAI-1 are one of the major disturbances of the hemostatic system in patients with diabetes and/or hypertension, and may have multiple interrelations with the important risk factors in the development of atherosclerosis. This study was performed to determine whether altered gene expression of PAI-1 occurs within the arterial wall, and thereby potentially contributing to the increase of cardiovascular risks associated with diabetes and/or hypertension. MATERIAL AND METHOD: The aortic vascular smooth muscle cells of the rat were exposed to 22 mM glucose, angiotensin II, and insulin increased PAI-1 mRNA expression with the use of Northern blotting were examined. Also examined were the effects of 22 mM glucose, angiotensin II and insulin on the growth of the rat's aortic smooth muscle cells by using MTT assay. RESULT: Twenty-two mM glucose treatment increased the PAI-1 mRNA expression in a time- and dose-dependent manner. Aniotensin II treatment synergistically increased the glucose-induced PAI-1 mRNA expression. In contrast, addition of insulin attenuated the increase of 22 mM glucose and angiotensin II induced PAI-1 mRNA expression. Furthermore, treatment of 22 mM glucose, angiotensin II and insulin resulted in a significant increase in cell numbers. This study demonstrated that 22 mM glucose and angiotensin II have a synergistic effect in stimulating the PAI-1 mRNA expression and in the cell growth of the rat's aortic smooth muscle cells.
CONCLUSION
Elevation of glucose and angiotensin II may be important risk factors in impairing fibrinolysis and developing atherosclerosis in diabetic patients.

Keyword

Glucose, Insulin; plasminogen activator; Smooth muscle relaxation; Plasminogen Activator Inhibitor-1

MeSH Terms

Angiotensin II*
Angiotensins*
Animals
Atherosclerosis
Blotting, Northern
Cell Count
Fibrinolysis
Gene Expression
Glucose*
Humans
Hypertension
Insulin*
Muscle, Smooth, Vascular*
Myocytes, Smooth Muscle
Plasma
Plasminogen Activator Inhibitor 1
Plasminogen Activators*
Plasminogen*
Rats*
Risk Factors
RNA, Messenger
Angiotensin II
Angiotensins
Glucose
Insulin
Plasminogen
Plasminogen Activator Inhibitor 1
Plasminogen Activators
RNA, Messenger