Prague hypertriglyceridemic (HTG) rats represent a suitable model of metabolic syndrome. We have established the set of F(2) hybrids derived from HTG and Lewis progenitors to investigate the relationship between respective polymorphism(s) of Igf2 gene and blood pressure (BP) or other cardiovascular phenotypes. HTG rats had elevated systolic BP and plasma triglycerides but lower plasma cholesterol compared to Lewis rats of both genders. In males, there was higher mean arterial pressure, diastolic BP and relative heart weight in HTG than in Lewis rats. The results obtained in the total population of F(2) hybrids indicated strong segregation of Igf2 genotype with plasma triglycerides. There was no segregation of Igf2 genotype with any BP component except BP changes occurring after the blockade of either renin-angiotensin system (RAS) or NO synthase. When F(2) population was analyzed according to gender, male F(2) progeny homozygous for HTG Igf2 allele had significantly higher plasma triglycerides and greater BP changes after NO synthase blockade than those homozygous for Lewis allele. On the contrary, male F(2) progeny homozygous for HTG Igf2 allele had significantly lower plasma cholesterol and smaller BP changes after RAS blockade. PCR analysis of Igf2 gene by using of microsatelite D1Mgh22 has shown polymorphism between HTG and Lewis rats. Sequence analysis of cDNA revealed insertion of 14 nucleotides in HTG gene. In conclusion, polymorphism in Igf2 gene may be responsible for differences in lipid metabolism between HTG and Lewis rats. It remains to determine how these abnormalities could be involved in BP regulation by particular vasoactive systems.
- MeSH
- financování organizované MeSH
- genetická vazba MeSH
- genotyp MeSH
- hypertriglyceridemie MeSH
- inbrední kmeny potkanů MeSH
- insulinu podobný růstový faktor II genetika MeSH
- krevní tlak fyziologie MeSH
- křížení genetické MeSH
- krysa rodu rattus MeSH
- ledviny anatomie a histologie MeSH
- lipidy krev MeSH
- mikrosatelitní repetice MeSH
- mutační analýza DNA MeSH
- potkani inbrední LEW MeSH
- srdce anatomie a histologie MeSH
- tělesná hmotnost genetika MeSH
- velikost orgánu genetika MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
High plasma triglyceride (TG) level is a major independent risk factor of coronary heart disease. A newly identified Apolipoprotein A5 (Apoa5) gene has been shown to play an important role in determining plasma TG concentrations in humans and mice. Prague hereditary hypertriglyceridemic (HTG) rats are a useful model of human hypertriglyceridemia and other symptoms of metabolic syndrome. Thus, the variation of Apoa5 gene and its expression were studied in this strain under normal conditions and after chronic fructose loading. Lewis and Wistar rats served as normotriglyceridemic controls. Plasma TG were significantly higher in HTG rats in comparison with both control strains. Sequence analysis of the rat Apoa5 gene revealed the existence of two introns. However, screening of the coding regions and intron-exon boundaries of Apoa5 gene did not indicate any mutation of this gene in HTG rats in comparison with Lewis and Wistar ones. Under the basal conditions the expression of Apoa5 was lower in all age groups of HTG rats compared to Wistar animals. Furthermore, during chronic fructose loading there were no significant changes of Apoa5 expression in HTG rats, although plasma TG levels rose 3-4 times within first two days of fructose loading and were increased during the whole period of fructose treatment. In conclusion, Apoa5 does not seem to be a genetic determinant of hypertriglyceridemia in HTG rats. The absence of significant changes in Apoa5 gene expression during chronic fructose-induced TG elevation excludes its major role in mechanisms compensating severe hypertriglyceridemia.
- MeSH
- apolipoproteiny A genetika krev metabolismus MeSH
- exprese genu fyziologie genetika MeSH
- financování vládou MeSH
- fruktosa metabolismus MeSH
- genetické jevy fyziologie genetika MeSH
- hypertriglyceridemie genetika krev metabolismus MeSH
- krysa rodu rattus MeSH
- metabolický syndrom genetika metabolismus MeSH
- sekvenční analýza metody statistika a číselné údaje MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
- Publikační typ
- abstrakt z konference MeSH