M Pravenec

..In the current study, we analyzed the role of folate deficiency in pathogenesis of the metabolic syndrome in the spontaneously hypertensive rat (SHR)...

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..To investigate the mechanism by which fat-specific transgenic expression of resistin affects fatty acid metabolism in the spontaneously hypertensive rat (SHR)...

..These findings are consistent with the hypothesis that increased CRP is more than just a marker of inflammation and can directly promote multiple features of the metabolic syndrome...

..These results suggest that with increasing age autocrine effects of resistin in fat tissue may predispose to diabetes in part by impairing insulin action in adipose tissue...

..These findings suggest that closely linked genes on Chr 19, or perhaps even a single gene with pleiotropic effects, influence the clustering of metabolic disturbances in the SHR-BN model...

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..The findings of the current study demonstrate that gene(s) with major effects on blood pressure and renal mass exist in the differential segment of chromosome 5 trapped within the new SHR.BN congenic strain...

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..To provide insight into genetics of essential hypertension, including discussion of methods used both in human and animal experimental studies and interpretation of results...

..In the present review, a genetic analysis of cardiovascular phenotypes studied at several levels of complexity in rat recombinant inbred strains is described...

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..The objective of the current study was to directly test for the presence of a blood pressure QTL on rat chromosome 2...

..The current findings extend homologies between rat chromosome 8, mouse chromosome 9, and human chromosomes 3q and 15q...

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..The current results demonstrate that rat chromosome 8 is largely homologous to mouse chromosome 9...

..The RI strains were phenotyped in multiple hemodynamic and metabolic traits. In the current study, we describe strain distribution patterns of 632 genetic markers...

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..Thus, genetic variation in genes on the Y chromosome may contribute to variation in blood pressure and lipid levels and may influence the risk for cardiovascular disease...

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..Our results provide direct evidence that Cd36 deficiency can promote defective insulin action and disordered fatty-acid metabolism in spontaneous hypertension...

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..BN-Lx rats...

..6+/-0.2 vs. 2.2+/-0.5 nnmol/g/2 h, P=0.02). These results provide evidence that visfatin exhibits important autocrine effects on sensitivity of liver cells to insulin action possibly through its effects on NAD biosynthesis...

..Despite relatively wide confidence intervals for mapping QTLs with modest effects in a small population of RI strains, this finding probably excludes the Fos as a positional candidate for CRG...

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..4) and is responsible for approximately 52% of genetic variation in CRH. This marker maps near Ace, Gh, and Ngfr positional candidate genes...

..9). This QTL region was designated Twq1 and associated with over 75% of genetic variability...

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..Candidate genes identified in these studies merit further investigation as potentially causative hypertension genes in SHR and human hypertension...

..54, P = 0.006) in adult rats. Our results suggest that predisposition toward a thrifty phenotype associated with decreased placental weight and restricted fetal growth is in part genetically determined...

..Within the close neighbourhood of the inserted Cd36 transgene, there are several genes known to be expressed in kidney, and so the influence of some regulatory sequences enhancing kidney expression of the Cd36 transgene can be envisaged...

..5 to 0.6). The verification of all these findings is in progress by means of double congenic strains which, in addition to the Lx gene, carry differential chromosome segments with putative modifiers...

..02+/-0.1 vs. 8.42+/-0.26 pmol.10(-3) cells, P=0.001). These findings provide evidence that CD36 regulates FA composition thereby affecting sensitivity to insulin action in 3T3-L1 adipocytes...

..These findings show that a primary defect in fatty acid transport can promote disordered carbohydrate metabolism in the SHR and show the power of advanced genome technologies for identifying QTL at the molecular level...

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..Owing to recent progress in the development of rat genomic resources, the pace of QTL identification and discovery of new disease mechanisms can be expected to accelerate in the near future...

..Expressions of TNFalpha, leptin and adiponectin were unaffected. In conclusions, our results indicate that acutely induced hyperlipidemia could influence the secretion of TNFalpha and resistin...

..3%) and the SHR-2 (SHR.BN-D2Rat171/D2Arb24) congenic strain (13.1+/-4.4%, p < .01) that are genetically identical except for a segment of chromosome 2 that was transferred onto the genetic background of the SHR from the BN strain...

..Our study confirms the validity of RI strains for the further genetic and physiological research of hypertension...

..This study evaluated the effect of telmisartan on insulin sensitivity, substrate utilization, selected plasma adipokines and their expressions in subcutaneous adipose tissue (SAT) in metabolic syndrome...

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..Both strategies could also be combined. In the current chapter, a method for derivation of "supersonic" congenic/conplastic rat strains is described...

..In this review, we offer a critical perspective on the use of gene expression profiling in hypertension research and discuss some emerging strategies for taking this technology beyond the limits of correlational and descriptive studies...

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..These results substantiate the value of the AFLP technology in increasing marker density in genetic maps...

..Thus, the salt-retaining aspects of some hypertensives may be, in large part, determined by genes responsible for renal excretion, the impact of which is predominant over the environment under acute challenge...

..Evidence was also found for the existence of a region on chromosome 8, which influences fluid intake in the SHR. The causative genes involved in these effects however remain to be determined...

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..In conclusion, the longer TA repeat unit in the promoter of Npr1 of SHR, in tandem with a putative cGMP responsive element, regulates the transcription of the Npr1 gene with consequences on diastolic blood pressure...

..Furthermore, we have established the utility of this experimental paradigm to identify loci responsible for cardiovascular regulation during stress in genetic hypertensive models...

..These findings provide direct pharmacogenetic evidence that in the SHR model, Cd36 is a key determinant of the insulin-sensitizing actions of a thiazolidinedione ligand of peroxisome proliferator-activated receptor gamma...

..The new genotypic information obtained also permitted further genetic characterization of the RI strain set including strain independence, genetic similarity among the individual strains, and non-syntenic associations between loci...

..These studies support the use of these rodent models to examine PE-CD36 interactions...

..We provide a detailed SNP map and demonstrate its utility for mapping of quantitative trait loci. This community resource is openly available and augments the genetic tools for this workhorse of physiological studies...

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..Further studies on the skin histology in affected rats demonstrated features consistent with a lanceolate hair mutation, providing further support for the crucial role of desmoglein 4 in hair shaft differentiation...

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..Finally, we present a set of principles that justify continuing and strengthening genetic studies in the rat model, and further development of genomic infrastructure for rat research...

..These characteristics make the rat an excellent model for studying phenotypic effects of structural variation in relation to human complex traits and disease...

..Taken together, these data implicate Ogn as a key regulator of LVM in rats, mice and humans, and suggest that Ogn modifies the hypertrophic response to extrinsic factors such as hypertension and aortic stenosis...

..The decrease of liver copper concentration after the high fat, high cholesterol diet is probably not caused by a decrease in whole hepatic copper content, but rather due to dietary-induced hepatomegaly...

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..The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease...

..We delineate the effects of genetic architecture on variation in gene expression and show the sensitivity of this experimental design to tissue sampling variability in large-scale eQTL studies...

..As muscle fatty acid oxidation is a major determinant of energy expenditure, we investigated the effects of telmisartan on skeletal muscle fatty acid oxidation in a rat model of the metabolic syndrome...

..The intronless Fabp6 segment, which might be a pseudogene of Fabp6, was localized on rat chromosome 15...