title: Calcineurin is critical for sodium-induced neointimal formation in normotensive and hypertensive rats.
abstract: It is well known that excessive intake of sodium chloride (sodium) is a risk factor for cardiovascular disease because it raises blood pressure. However, sodium loading reportedly promotes cardiovascular disease independently of its effect on blood pressure. To examine the mechanisms by which sodium loading promotes vascular inflammation independently of its effect on blood pressure, we examined the role of calcineurin in sodium loading-induced vascular inflammation using a wire injury model of the rat femoral artery. Calcineurin mRNA expression in the wire-injured femoral artery was significantly higher in sodium-loaded normotensive rats, such as Wistar-Kyoto (WKY) rats, than that in control WKY rats. Neointimal formation was also significantly enhanced in sodium-loaded WKY rats compared with control WKY rats. Gene transfer of an adenovirus expressing a dominant negative mutant of calcineurin (AdCalADeltaC92Q) significantly suppressed neointimal formation in sodium-loaded WKY rats to a level similar to that observed in control WKY rats. Calcineurin expression and neointimal formation were more significantly enhanced in hypertensive rats, such as spontaneously hypertensive rats (SHRs), than those in control WKY rats. AdCalADeltaC92Q infection significantly suppressed neointimal formation in SHRs to a level similar to that observed in control WKY rats. These results suggest that sodium loading promotes neointimal formation, even in normotensive rats, and that hypertension further stimulates neointimal formation. These results also suggest that calcineurin plays a pivotal role in this process.
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Takeda
authors.forename: Etsu
authors.initials: E
authors.lastname: Suzuki
authors.forename: Masao
authors.initials: M
authors.lastname: Takahashi
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Oba
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nishimatsu
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kimura
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nagano
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Hirata
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001794:Blood Pressure; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000293:injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006973:Hypertension / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009154:Mutation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D013997:Time Factors; D017539:Tunica Intima / Q000378:metabolism* / Q000473:pathology; D014657:Vasculitis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D019703:Calcineurin