Key result
Compared with SHR, the PD5 congenic strain with a mutant Plzf allele showed significantly reduced systolic blood pressure (~15 mm Hg, P=0.002), amelioration of LVH (P<0.00001), and reduced fibrosis.
p-value: p=0.002
The Plzf gene is identified as a prominent candidate gene regulating blood pressure, left ventricular hypertrophy, and cardiac fibrosis in the spontaneously hypertensive rat model.
Mutant Plzf reduces BP, LVH, and fibrosis in SHR; leaves open its relevance as a therapeutic target in human hypertension.
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.
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Liška et al. (2013) studied Hypertension, left ventricular hypertrophy, and interstitial fibrosis. PD5 congenic strain (mutant Plzf allele) vs. Spontaneously hypertensive rat (SHR) was evaluated on Systolic blood pressure, left ventricular hypertrophy, and interstitial fibrosis (p=0.002). Compared with SHR, the PD5 congenic strain with a mutant Plzf allele showed significantly reduced systolic blood pressure (~15 mm Hg, P=0.002), amelioration of LVH (P<0.00001), and reduced fibrosis.
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