title: Plzf as a candidate gene predisposing the spontaneously hypertensive rat to hypertension, left ventricular hypertrophy, and interstitial fibrosis.
abstract: BACKGROUND
  The spontaneously hypertensive rat (SHR) is the most widely used model of essential hypertension and is susceptible to left ventricular hypertrophy (LVH) and myocardial fibrosis. Recently, a quantitative trait locus (QTL) that influences heart interstitial fibrosis was mapped to chromosome 8. Our aim was to dissect the genetic basis of this QTL(s) predisposing SHR to hypertension, LVH, and interstitial fibrosis.
  
  
  METHODS
  Hemodynamic and histomorphometric analyses were performed in genetically defined SHR.PD-chr.8 minimal congenic strain (PD5 subline) rats.
  
  
  RESULTS
  The differential segment, genetically isolated within the PD5 subline, spans 788kb and contains 7 genes, including the promyelocytic leukemia zinc finger (Plzf) gene that has been implicated in hypertrophy and cardiac fibrosis. Mutant Plzf allele contains a 2,964-bp deletion in intron 2. The PD5 congenic strain, when compared with the SHR, showed significantly reduced systolic blood pressure by approximately 15mm Hg (P = 0.002), amelioration of LVH (0.23±0.02 vs. 0.39±0.02g/100g body weight; P < 0.00001), and reduced interstitial fibrosis (17,478±1,035 vs. 41,530±3,499 μm(2); P < 0.0001). The extent of amelioration of LVH and interstitial fibrosis was disproportionate to blood pressure decrease in congenic rats, suggesting an important role for genetic factors. Cardiac expression of Plzf was significantly reduced in prehypertensive (8 and 21 days) congenic animals compared with controls.
  
  
  CONCLUSIONS
  These results provide compelling evidence of a significant role for genetic factors in regulating blood pressure, LVH, and cardiac fibrosis and identify mutant Plzf as a prominent candidate gene.
authors: Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague, Czech Republic.
authors: František
authors: F
authors: Liška
authors: Massimiliano
authors: M
authors: Mancini
authors: Michaela
authors: M
authors: Krupková
authors: Blanka
authors: B
authors: Chylíková
authors: Drahomíra
authors: D
authors: Křenová
authors: Ondřej
authors: O
authors: Šeda
authors: Jan
authors: J
authors: Šilhavý
authors: Petr
authors: P
authors: Mlejnek
authors: Vladimír
authors: V
authors: Landa
authors: Václav
authors: V
authors: Zídek
authors: Giulia
authors: G
authors: d' Amati
authors: Michal
authors: M
authors: Pravenec
authors: Vladimír
authors: V
authors: Křen
mesh_terms: D000818:Animals; D020296:Animals, Congenic; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006439:Hemodynamics / Q000235:genetics; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000473:pathology*; D010641:Phenotype; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D040641:Quantitative Trait Loci; D051381:Rats; D011918:Rats, Inbred SHR; D013997:Time Factors
chemical_list: D004268:DNA-Binding Proteins; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C534029:ZBTB16 protein, rat
keywords: Plzf (promyelocytic leukemia zinc finger) gene.; blood pressure; hypertension; left ventricular hypertrophy; myocardial interstitial fibrosis; quantitative trait locus; spontaneously hypertensive rat