P. Etienne et al., PHENOTYPE MODULATION IN PRIMARY CULTURES OF AORTIC SMOOTH-MUSCLE CELLS FROM STREPTOZOTOCIN-DIABETIC RATS, Differentiation, 63(4), 1998, pp. 225-236
Diabetes mellitus is a major risk factor for atherosclerosis. In ather
osclerotic lesions, arterial smooth muscle cells (SMC) change from a c
ontractile to a synthetic phenotype characterized by active proliferat
ion. A similar phenotype modulation occurs in vitro when isolated arte
rial SMC are grown in culture and is characterized by both changes in
cell morphology and a typical switch in actin isoform expression. In t
his study, we examined the influence of streptozotocin(STZ)-induced di
abetes on the differentiation state and the phenotype modulation of In
troduction cultured rat aortic SMC. We used transmission electron micr
oscopy to study the fine structure of STZ-diabetic and non-diabetic SM
C in primary culture and immunological methods for the determination o
f the proportions of alpha-smooth muscle actin (alpha-SM) and nonmuscl
e beta-actin (beta-NM) isoforms. Cultured STZ-diabetic SMC exhibited a
large cytoplasmic volume, rich in rough endoplasmic reticulum, when c
ompared with cultured non-diabetic SMC. alpha-SM, organized in stress
fibers, was less homogeneously and abundantly distributed and by contr
ast, PNM was more abundant in STZ-diabetic than in non-diabetic SMC. C
ytofluorimetric analyses demonstrated that the alpha-SM content was re
duced in freshly STZ-diabetic SMC. Furthermore, during logarithmic gro
wth of cultured SMC, the decrease of alpha-SM was more important in ST
Z-diabetic than in non-diabetic SMC. Immunoblotting of actin isoforms
confirmed that expression of beta-NM was more important in STZ-diabeti
c than in non-diabetic SMC even in freshly isolated cells. The results
suggest that SMC from STZ-diabetic rats express a more dedifferentiat
ed state and undergo a more rapid phenotypic modulation in primary cul
tures than SMC from non-diabetic rats. Therefore, diabetes could induc
e changes in the phenotype of arterial SMC which might be associated w
ith the onset or progression of the atherogenic process.