Influence of protamine on adhesion, chemotaxis and proliferation of human vascular smooth muscle cells.

Abstract:

:It has been shown that, in streptozotocin diabetic rats, protamine-retarded insulin administered in vivo stimulates intimal hyperplasia in balloon-injured carotid artery. The aim of this study was to evaluate the influence of protamine on cultured human vascular smooth muscle cells (h VSMC), by observing its effects on adhesion, chemotaxis and proliferation. hVSMC were isolated during abdominal surgery, cultured and utilized at passages 6-10. We observed that protamine stimulates: 1) cell adhesion in the concentration range 0.04-20 micrograms/ml (analysis of variance, ANOVA, p < 0.0001); 2) cell chemotaxis in the absence of fetal calf serum (FCS) in the concentration range 1-200 micrograms/ml (ANOVA, p < 0.0001) and in the presence of 1% FCS in the concentration range 5-200 micrograms/ml (ANOVA, p < 0.0001), further enhancing the chemotaxis induced by 10% FCS in the concentration range 20-200 micrograms/ml (ANOVA, p < 0.0001); 3) cell proliferation and 3H-thymidine incorporation from 1 to 5 micrograms/ml (ANOVA, p < 0.0001); 4) cell c-fos oncoprotein nuclear expression. We also observed that protamine effects on chemotaxis, proliferation and c-fos expression are inhibited by heparin that human insulin stimulates cell proliferation and 3H-thymidine incorporation (ANOVA, p < 0.0001) at concentrations equal to or greater than 480 pmol/l and that these effects of insulin persist in the presence of protamine. In conclusion, protamine influences hVSMC behaviour by interfering with biological functions involved in atherogenesis. The concentrations used in this short-term in vitro study were higher than those probably occurring in vivo in patients chronically treated by protamine-retarded insulin preparations: further studies, therefore, are needed to evaluate the safety of protamine as a retardant of insulin action in vivo.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Cavalot F,Russo I,Mattiello L,Anfossi G,Massucco P,Mularoni E,Hahn AW,Trovati M

doi

10.1007/s001250050644

subject

Has Abstract

pub_date

1997-01-01 00:00:00

pages

67-75

issue

1

eissn

0012-186X

issn

1432-0428

journal_volume

40

pub_type

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