Enhanced expression of salusin-β contributes to progression of atherosclerosis in LDL receptor deficient mice

Atherosclerosis is an important underlying pathology of cardiovascular diseases. The aim of this study was to observe the expression of salusin-β, a new vasoactive peptide, in vascular tissues of low-density lipoprotein receptor deficient ([LDLR.sup.-/-]) mice, and to evaluate the effect of salusin-β on the development of atherosclerosis in [LDLR.sup.-/-] mice. Six-week-old, male [LDLR.sup.-/-] mice were subcutaneously injected with salusin-β or the vehicle, once a day for 12 weeks. The expressions of salusin-β in both mRNA and peptide levels were determined by reverse transcription--polymerase chain reaction, Western blot, and immunohistochemistry. Atherosclerotic lesions were analyzed by staining with hematoxylin and eosin or oil red O. Our results showed that expression of salusin-β in mRNA and salusin-β peptide levels were enhanced in [LDLR.sup.-/-] mice. Subcutaneous injection of salusin-β significantly aggravated the atherosclerotic lesions, and increased lipid deposits in the arteries of [LDLR.sup.-/-] mice. Moreover, salusin-β significantly increased the serum level of low-density lipoprotein cholesterol, but not total cholesterol, triglycerides, or high-density lipoprotein cholesterol. These results suggest that the enhanced expression of salusin-β contributes to progression of atherosclerosis in [LDLR.sup.-/-] mice by up-regulating the serum low-density lipoprotein cholesterol level. This study provides a potential therapeutic target for the prevention and treatment of atherosclerosis. Key words: atherosclerosis, salusin-β, peptide, mice. L'atherosclerose est une pathologie importante, sous-jacente aux maladies cardiovasculaires. Le but de cette etude etait d'observer l'expression de la salusine-β, un nouveau peptide vasoactif, dans les tissus vasculaires de souris depourvues de recepteur des lipoproteines de faible densite (LDLR -/-). Des souris males [LDLR.sup.-/-] de 6 semaines ont recu une injection sous-cutanee quotidienne de salusine-β ou de vehicule seul pendant 12 semaines. L'expression de la salusine-b et de son ARNm a ete determinee par buvardage, immunohistochimie et d'amplification en chaine par polymerase--transcriptase inverse. Les lesions atherosclereuses ont ete analysees par coloration a l'hematoxyline et eosine (H&E) et au oil red O. Nos resultats ont montre que l'expression de la salusine-b et de son ARNm etait augmentee chez les souris [LDLR.sup.-/-]. Une injection sous-cutanee de salusine-b aggravait significativement les lesions atherosclereuses et augmentait les depots lipidiques dans les arteres des souris [LDLR.sup.-/-]. De plus, la salusine-β augmentait significativement les niveaux seriques de lipoproteine a faible densite choleterol, mais pas ceux des cholesterol total, triglycerides et lipoproteine de haute densite cholesterol. Ces resultats suggerent que l'augmentation de l'expression de la salusine-β contribue a la progression de l'atherosclerose chez les souris [LDLR.sup.-/-] en regulant a la hausse le niveau serique de lipoproteine a faible densite choleterol. Cette etude identifie une cible therapeutique potentielle pour la prevention et le traitement de l'atherosclerose. Mots-cles : atherosclerose, salusine-β, peptide, souris. [Traduit par la Redaction]
Introduction Salusins constitute a new class of vasoactive peptides originally identified by Shichiri et al. in 2003, consisting of 2 related peptides of 28 and 20 amino acids, designated salusin-α [...]