A quantitative trait locus for aortic smooth muscle cell number acting independently of blood pressure: implicating the angiotensin receptor AT1B gene as a candidate.
Vascular hyperplasia may be involved in the remodeling of vasculature. It was unknown whether there were genetic determinants for aortic smooth muscle cell number (SMCN) and, if so, whether they acted independently of those for blood pressure (BP). To unravel this issue, we utilized congenic strains previously constructed for BP studies. These strains were made by replacing various chromosome 2 segments of the Dahl salt-sensitive (S) rat with those of the Milan normotensive rat (MNS). We measured and compared SMCN in aortic cross-sectional areas and BPs of these strains. Consequently, a quantitative trait locus (QTL) for SMCN was localized to a chromosome region not containing a BP QTL, but harboring the locus for the angiotensin II receptor AT1B (Agtr1b). Agtr1b became a candidate for the SMCN QTL because 1) two significant mutations were found in the coding region between S and all congenic strains possessing the MNS alleles, and 2) contractile responses to angiotensin II were significantly and selectively reduced in congenic rats harboring the MNS alleles of the SMCN QTL compared with S rats. The current investigation presents the first line of evidence that a QTL for aortic SMCN exists, and it acts independently of QTLs for BP. The relevant congenic strains developed therein potentially provide novel mammalian models for the studies of vascular remodeling disorders.
Dutil
Julie
J
Research Centre-Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec, Canada.
Eliopoulos
Vasiliki
V
Marchand
Eve-Lyne
EL
Devlin
Alison M
AM
Tremblay
Johanne
J
Prithiviraj
Kalyani
K
Hamet
Pavel
P
Migneault
Annik
A
deBlois
Denis
D
Deng
Alan Y
AY
D000818:Animals; D001011:Aorta; D001483:Base Sequence; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology*; D002874:Chromosome Mapping; D017931:DNA Primers; D005819:Genetic Markers; D006973:Hypertension / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000502:physiology* / Q000503:physiopathology; D009154:Mutation; D040641:Quantitative Trait Loci; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D012016:Reference Values
D017931:DNA Primers; D005819:Genetic Markers; D044140:Receptor, Angiotensin, Type 1