Differential Genetic Basis for Pre-Menopausal and Post-Menopausal Salt-Sensitive HypertensionReportar como inadecuado

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Essential hypertension affects 75% of post-menopausal women in the United States causing greater cardiovascular complications compared with age-matched men and pre-menopausal women. Hormone replacement and current anti-hypertensive therapies do not correct this post-menopausal increased risk suggesting a distinct pathogenic framework. We investigated the hypothesis that distinct genetic determinants might underlie susceptibility to salt sensitive hypertension in pre-menopausal and post-menopausal states. To determine whether distinct genetic loci contribute to post-menopausal salt-sensitive hypertension, we performed a genome-wide scan for quantitative trait loci QTLs affecting blood pressure BP in 16-month old post-menopausal F2 Dahl S×R-intercross female rats characterized for blood pressure by radiotelemetry. Given identical environments and high salt challenge, post-menopausal BP levels were significantly higher than observed in pre-menopausal post-menopausal versus pre-menopausal SBP, P<0.0001 and ovariectomized post-menopausal versus ovariectomized SBP, P<0.001 F2-intercross female rats. We detected four significant to highly significant BP-QTLs BP-pm1 on chromosome 13, LOD 3.78; BP-pm2 on chromosome 11, LOD 2.76; BP-pm3 on chromosome 2, LOD 2.61; BP-pm4 on chromosome 4, LOD 2.50 and two suggestive BP-QTLs BP-pm5 on chromosome 15, LOD 2.37; BP-f1 on chromosome 5, LOD 1.65, four of which BP-pm2, BP-pm3, BP-pm4, BP-pm5 were unique to this post-menopausal cohort. These data demonstrate distinct polygenic susceptibility underlying post-menopausal salt-sensitive hypertension providing a pathway towards the identification of mechanism-based therapy for post-menopausal hypertension and ensuing target-organ complications.

Autor: Victoria L. M. Herrera, Khristine A. Pasion, Ann Marie Moran, Nelson Ruiz-Opazo

Fuente: http://plos.srce.hr/


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