Tissue-specific modulation of [formula omitted]-adducin transcripts in Milan hypertensive rats

Abstract

Genetic variants in Adducins, a family of cytoskeleton proteins (α, β, and γ) encoded by three genes, have been associated with primary hypertension in humans and in Milan hypertensive (MHS) rats. The present paper describes the identification of a rat β4 alternative splicing isoform differing from β subunit for an in-frame insertion of 18 amino acids and showing a polymorphic site (R592W) between MHS and its normotensive control (MNS). Furthermore, we established a quantitative real-time PCR assay for analyzing the tissue expression of adducin gene family and determining whether any subunit transcript demonstrates altered expression during the development of MHS hypertension, especially in tissues relevant for the control of cardiovascular phenotypes (i.e., kidney, left ventricle, and large arteries). Among the three adducins only β transcripts were modulated, in a tissue-specific manner, during the development of hypertension in MHS, compared to age-matched MNS controls. A 43% decrease in renal outer medulla was already present at the prehypertensive phase; a 70% decrease in femoral artery and 66% increase in left ventricle were observed after the development of hypertension. Surprisingly β4-Add, which is a minor component of total β transcripts, is drastically reduced up to 88% in all MHS tissues. Alteration in β-Add expression levels may account, at least in part, for the observed phenotypic changes in MHS hypertension.