title: Genetic predisposition to albuminuria is associated with increased arterial stiffness: role of elastin.
abstract: OBJECTIVE
  The Munich Wistar Frömter (MWF) rat strain represents an experimental model to study cardiovascular alterations under conditions of progressive albuminuria. The aim of this study was to evaluate the association between genetic predisposition to albuminuria and the development of arterial stiffness and/or vascular remodelling.
  
  
  METHODS
  Experiments were performed in mesenteric arteries from 12-week-old MWF, Wistar Kyoto (WKY) and consomic MWF-6(SHR) and MWF-8(SHR) rats in which chromosomes 6 or 8 associated with albuminuria from MWF were replaced by the respective chromosome from spontaneously hypertensive rats (SHR).
  
  
  RESULTS
  Incremental distensibility, wall stress and strain were reduced, and arterial stiffness was significantly increased in albuminuric MWF compared with WKY. Albuminuria suppression in both consomic strains was associated with lower β-values in MWF-8(SHR) and MWF-6(SHR) compared with MWF. Moreover, elastin content was significantly lower in MWF external elastic lamina compared with WKY and both consomic strains. In addition, a reduction in arterial external and internal diameter and cross-sectional area was detected in MWF compared with WKY, thus exhibiting an inward hypotrophic remodelling. However, these alterations remained unchanged in both consomic strains.
  
  
  CONCLUSIONS
  These data demonstrate that albuminuria in MWF is associated with increased arterial stiffness due to a reduction of elastin content in the external elastic lamina. Moreover, inward hypotrophic remodelling in MWF is not directly associated with albuminuria. In contrast, we demonstrated that two major genetic loci affect both the development of albuminuria and arterial stiffness, thus linking albuminuria and impairment of mechanical properties of resistance arteries.
authors.affiliation: Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU - San Pablo, Madrid, Spain.
authors.forename: M
authors.identifier: http://orcid.org/0000-0002-6366-8214
authors.initials: M
authors.lastname: Gil-Ortega
authors.affiliation: Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU - San Pablo, Madrid, Spain.
authors.forename: C F
authors.initials: CF
authors.lastname: García-Prieto
authors.affiliation: Instituto Pluridisciplinar and Facultad de Farmacia, Universidad Complutense, Madrid, Spain.|Instituto de Investigación imas12, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Ruiz-Hurtado
authors.affiliation: Instituto Pluridisciplinar and Facultad de Farmacia, Universidad Complutense, Madrid, Spain.|Department of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Steireif
authors.affiliation: Departamento de Fisiología, Universidad Autónoma, Madrid, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: González
authors.affiliation: Department of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schulz
authors.affiliation: Department of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Kreutz
authors.affiliation: Instituto Pluridisciplinar and Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
authors.forename: M S
authors.initials: MS
authors.lastname: Fernández-Alfonso
authors.affiliation: Departamento de Fisiología, Universidad Autónoma, Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Arribas
authors.affiliation: Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU - San Pablo, Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Somoza
mesh_terms: D000419:Albuminuria / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D004549:Elastin / Q000502:physiology*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D008297:Male; D008638:Mesenteric Arteries / Q000503:physiopathology; D009924:Organ Culture Techniques; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D059289:Vascular Stiffness / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D004549:Elastin