Genes Encoding Atrial and Brain Natriuretic Peptides as Candidates for Sensitivity to Brain Ischemia in Stroke-Prone Hypertensive Rats

Brosnan, M J; Clark, James S.; Jeffs, Baxter; Negrin, Cervantes D.; Vooren, Pascale Van; Arribas, Silvia M.; Carswell, Hilary V O; Aitman, Timothy J.; Szpirer, Claude; Macrae, I Mhairi; Dominiczak, Anna F.

doi:10.1161/01.hyp.33.1.290

Cited by 38 publications

(29 citation statements)

References 31 publications

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“…A recent study 34 that examines the possible role of ANP in stroke in the rat and fails to find evidence for such a contribution is actually quite consistent with our observations: in this study, SHRSP and WKY rats subjected to middle cerebral artery occlusion showed no differences in brain ANP expression. Of note, there was no difference between the ANP genes of the two strains used with regard to sequence, structure, and functional parameters, as demonstrated previously.…”

Section: Discussionsupporting

confidence: 91%

“…Of note, there was no difference between the ANP genes of the two strains used with regard to sequence, structure, and functional parameters, as demonstrated previously. 34 An earlier, erroneous interpretation that stroke in an intercross of SHRSP and WKY rats was linked to the ANP locus 35 was indeed corrected by additional data on chromosomal localization of ANP in this recent report. 34 Although the present data support the notion that ANP may indeed be a candidate gene for contribution to stroke given its localization within the stroke-linked locus STR2, final validation of this result must be based on congenic and positional cloning experiments, which are in progress.…”

Section: Discussionmentioning

confidence: 82%

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Altered Structure, Regulation, and Function of the Gene Encoding the Atrial Natriuretic Peptide in the Stroke-Prone Spontaneously Hypertensive Rat

Rubattu

Lee‐Kirsch

DePaolis

et al. 1999

Circulation Research

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Abstract-Through the genotype/phenotype cosegregation analysis of an F 2 intercross, from the crossbreeding of stroke-prone spontaneously hypertensive rats (SHRSP) and stroke-resistant spontaneously hypertensive rats (SHR), we previously identified a quantitative trait locus for stroke on rat chromosome 5 (STR2) that colocalized with the genes encoding atrial and brain natriuretic peptides (ANP and BNP) and conferred a stroke-delaying effect. To further characterize ANP and BNP as candidates for stroke, we performed additional studies. Comparative sequence analysis revealed point mutations in both the coding and regulatory regions of ANP, whereas no interstrain differences were found for BNP. In in vitro studies in COS-7 and AtT-20 cells that were performed to test the relevance of a G3 A substitution at position 1125, a Gly3 Ser transposition in the SHRSP pro-ANP peptide resulted in different posttranslational processing of the SHRSP ANP gene product that was also associated with higher cGMP production (PϽ0.05). Furthermore, an analysis of a 5Ј end mutation affecting a PEA2 regulatory binding site in the 5Ј untranslated regulatory sequence of SHRSP ANP demonstrated a significantly lower ANP promoter activation in endothelial cells (PϽ0.05 versus the SHR ANP). In addition, the expression of ANP was significantly reduced in the brain, but not in the atria, of SHRSP compared with SHR (PϽ0.0001). No differences were detected with regard to BNP expression. The present results reveal substantial differences in ANP, but not BNP, structure and product among SHR and SHRSP, which supports a role of ANP in the pathogenesis of stroke in the SHRSP animal model. (Circ Res. 1999;85:900-905.)

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 82%

Altered Structure, Regulation, and Function of the Gene Encoding the Atrial Natriuretic Peptide in the Stroke-Prone Spontaneously Hypertensive Rat

Rubattu

Lee‐Kirsch

DePaolis

et al. 1999

Circulation Research

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“…Plasma levels of BNP have previously been described as elevated in the acute phase of stroke, 16,17 and some authors have suggested that BNP levels are correlated with neurologic deficits. 17,18 However, although in our study BNP also showed a slight correlation with the NIHSS score, it remained an independent predictor of cardioembolic etiology after correcting for stroke severity and extent.…”

Section: Bnp and Dd For Cardioembolic Strokementioning

confidence: 99%

Etiologic Diagnosis of Ischemic Stroke Subtypes With Plasma Biomarkers

Montaner¹,

Perea-Gainza²,

Delgado³

et al. 2008

Stroke

268

212

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Background and Purpose-Because there is no biologic marker offering precise information about stroke etiology, many patients receive a diagnosis of undetermined stroke even after all available diagnostic tests are done, precluding correct treatment. Methods-To examine the diagnostic value of a panel of biochemical markers to differentiate stroke etiologies, consecutive acute stroke patients were prospectively evaluated. Brain computed tomography, ultrasonography, cardiac evaluations, and other tests were done to identify an etiologic diagnosis according to TOAST classification. Blood samples were drawn on Emergency Department arrival (Ͻ24 hours) to test selected biomarkers: C-reactive protein, D-dimer, soluble receptor for advanced glycation end products, matrix metalloproteinase-9, S-100b, brain natriuretic peptide (BNP), neurotrophin-3, caspase-3, chimerin, and secretagogin (assayed by ELISA). 6.7, PϽ0.001). A model combining clinical and biochemical data had a sensitivity of 66.5% and a specificity of 91.3% for predicting cardioembolism. Conclusions-Using a combination of biomarkers may be a feasible strategy to improve the diagnosis of cardioembolic stroke in the acute phase, thus rapidly guiding other diagnostic tests and accelerating the start of optimal secondary prevention. Results-Of

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“…39 It should be noted that this QTL colocalizes with the blood pressure QTL observed in studies on Dahl S rats. 19,26 It appears that there are 2 separate QTL for stroke on rat chromosome 5 40 and a blood pressure QTL that might be either related or unrelated to one of these stroke QTL. 19 A current comprehensive review by Rapp 19 provided a unifying speculation to explain the coexistence and colocalization of the blood pressure-independent stroke QTL and the blood pressure QTL on rat chromosome 5.…”

Section: Experimental Models Of Genetic Hypertensionmentioning

confidence: 99%

Genes and Hypertension

et al. 2000

Self Cite

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Abstract-Human essential hypertension is a complex, multifactorial, quantitative trait under a polygenic control. Several strategies have been developed over the last decade to dissect genetic determinants of hypertension. Of these, the most successful have been studies that identified rare mendelian syndromes in which a single gene mutation causes high blood pressure. The attempts to identify multiple genes, each with a small contribution to the common polygenic form of hypertension, have been less successful. Several laboratories focused their attention on rat models of genetic hypertension, which can be considered as a reductionist paradigm for human disease. Using numerous crosses between hypertensive and normotensive strains, investigators identified several quantitative trait loci (QTL) for blood pressure subphenotypes and for cardiovascular complications such as left ventricular hypertrophy, kidney failure, stroke, and insulin resistance. Furthermore, congenic strains have been produced to confirm the existence of some of these QTL and to narrow down the chromosomal regions of interest. A number of interesting strategies have been developed, including a "speed" congenic strategy perfected by our group in Glasgow. However, the limit of congenic strategy is estimated at 1 cM, which corresponds to 2ϫ10 6 base pairs of DNA and Ϸ50 candidate genes. It is envisaged that gene expression profiling with cDNA microarrays might allow a quick progression toward the gene identification within cardiovascular QTL. In parallel experimental effort, several laboratories have been developing gene transfer/therapy strategies with adenoviral or adeno-associated viral vectors used, for example, to overexpress protective vascular genes such as vascular endothelial growth factor or endothelial nitric oxide synthase. It is anticipated that further developments in positional cloning of susceptibility and severity genes in hypertension and its complications will lead to a direct transfer of these discoveries to essential hypertension in humans and will ultimately produce novel targets for local and systemic gene therapy in cardiovascular disease. Key Words: genes Ⅲ rats Ⅲ stroke Ⅲ endothelium Ⅲ hypertension, essential H uman essential hypertension is a typical example of a complex, multifactorial, and polygenic trait. It is most likely that there are several causal genes, which together contribute to between 30% and 50% of the variation in blood pressure among individuals. 1 These genetic determinants interact with environmental factors such as, for example, dietary salt to produce the final disease phenotype. Despite very significant recent progress in genomic and statistical tools, the genetic dissection of human essential hypertension still provides a major challenge. 2 Three main lines of investigation have been developed so far. These include linkage analysis in families segregating for rare, mendelian forms of hypertension, candidate gene approaches, and genome-wide scanning strategies. Of the above approaches, the search for...

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Genes Encoding Atrial and Brain Natriuretic Peptides as Candidates for Sensitivity to Brain Ischemia in Stroke-Prone Hypertensive Rats

Cited by 38 publications

References 31 publications

Altered Structure, Regulation, and Function of the Gene Encoding the Atrial Natriuretic Peptide in the Stroke-Prone Spontaneously Hypertensive Rat

Altered Structure, Regulation, and Function of the Gene Encoding the Atrial Natriuretic Peptide in the Stroke-Prone Spontaneously Hypertensive Rat

Etiologic Diagnosis of Ischemic Stroke Subtypes With Plasma Biomarkers

Genes and Hypertension

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