Insulin-like growth factor binding proteins in arterial hypertension: relationship to left ventricular hypertrophy

Abstract

OBJECTIVE: It was reported previously that circulating insulin-like growth factor I levels are abnormally elevated in patients with essential hypertension and left ventricular hypertrophy. Tissue availability of the factor depends on the distribution of the circulating bound factor between its high- and low-molecular mass binding proteins, only the latter being able to cross the endothelium. The aim of this study was to investigate whether the presence of the different serum binding proteins is altered in patients with essential hypertension and left ventricular hypertrophy.

DESIGN: The study was performed in 30 never-treated patients with essential hypertension and 30 age- and sex-matched normotensive subjects. Patients were separated into two groups according to the presence or the absence of echocardiographically determined left ventricular hypertrophy.

METHODS: Plasma insulin-like growth factor I levels were determined by specific radioimmunoassay. The different molecular forms of its serum binding proteins were analysed by Western blotting using [125I]-labelled insulin-like growth factor I. A densitometric scanning of the blots was performed to analyse the quantitative relationships between the different forms of binding proteins.

RESULTS: Insulin-like growth factor I levels were significantly higher in the hypertensive patients with than in the hypertensive patients without left ventricular hypertrophy or in the normotensive subjects. Compared with the normotensive subjects, both hypertensive patients subgroups exhibited increased high-molecular mass binding protein type 3 and decreased low-molecular mass binding proteins types 1 and 2. However, changes in the binding proteins were more marked in the hypertensive patients without than in the hypertensive patients with left ventricular hypertrophy. Accordingly, the ratio of low- to high-molecular mass binding proteins (an index of insulin-like growth factor I bioavailability) was higher in the hypertensive patients with than in the hypertensive patients without left ventricular hypertrophy.

CONCLUSIONS: These results show that the distribution of the molecular forms of serum insulin-like growth factor binding proteins is altered in patients with essential hypertension, independently of insulin-like growth factor I levels. This suggests that regulation of the binding proteins is abnormal in essential hypertension. Whether the tissue availability of circulating insulin-like growth factor I is higher in hypertensive patients with than in hypertensive patients without left ventricular hypertrophy merits further investigation.