ArticleCirculation. Cardiovascular genetics2014
Hypertensive renal injury is associated with gene variation affecting immune signaling.
Article in Circulation. Cardiovascular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Polygenic genetic variation affecting antibody formation underlies hypertensive renal injury in the stroke-prone spontaneously hypertensive rat.American journal of physiology. Renal physiology · 2023Article
- A New Approach for the Development of Multiple Cardiovascular Risk Factors in Two Rat Models of Hypertension.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Sex differences in hypertension: lessons from spontaneously hypertensive rats (SHR).Clinical science (London, England : 1979) · 2021Review
- Genetic susceptibility of hypertension-induced kidney disease.Physiological reports · 2021Review
- Article
- Germ-line genetic variation in the immunoglobulin heavy chain creates stroke susceptibility in the spontaneously hypertensive rat.Physiological genomics · 2019Article
- Adaptive Immunity in Hypertension.Current hypertension reports · 2019Review
- Targeted disruption of regulated endocrine-specific protein ( Resp18) in Dahl SS/Mcw rats aggravates salt-induced hypertension and renal injury.Physiological genomics · 2018Article
- Susceptibility to Hypertensive Renal Disease in the Spontaneously Hypertensive Rat Is Influenced by 2 Loci Affecting Blood Pressure and Immunoglobulin Repertoire.Hypertension (Dallas, Tex. : 1979) · 2018Article
- Genetic Susceptibility to Hypertension-Induced Renal Injury.Hypertension (Dallas, Tex. : 1979) · 2018Article
- Renal inflammation and injury are associated with lymphangiogenesis in hypertension.American journal of physiology. Renal physiology · 2017Article
- Mycophenolate mofetil prevents cerebrovascular injury in stroke-prone spontaneously hypertensive rats.Physiological genomics · 2017Article
- Defective Store-Operated Calcium Entry Causes Partial Nephrogenic Diabetes Insipidus.Journal of the American Society of Nephrology : JASN · 2016Article
- Evidence for a link between gut microbiota and hypertension in the Dahl rat.Physiological genomics · 2015Article
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Authors and funding
9 authors.
Funding
Abstract
backgroundThe spontaneously hypertensive rat (SHR) strain exists in lines that contrast strongly in susceptibility to renal injury in hypertension. These inbred lines share common ancestry, and only 13% of their genomes arise from different ancestors. METHODS AND
resultsWe used next gen sequencing to detect natural allelic variation in 5 genes of the immunoreceptor signaling pathway (IgH, Dok3, Src, Syk, and JunD) that arise from different ancestors in the injury-prone SHR-A3 and the resistant SHR-B2 lines. We created an intercross between these lines, and in the F2 progeny, we observed that the inheritance of haplotype blocks containing the SHR-A3 alleles of these 5 genes correlated with increased albuminuria and histological measures of renal injury. To test whether accumulated genetic variation in this pathway may create a therapeutic target in hypertensive renal injury, rats of both lines were treated with the immunosuppressant mycophenolate mofetil (MMF). MMF reduced proteinuria (albumin to creatinine ratio) from 6.6 to 1.2 mg/mg (P<0.001) in SHR-A3. Glomerular injury scores were reduced in MMF-treated SHR-A3 from 1.6 to 1.4 (P<0.002). Tubulo-interstitial injury was reduced in MMF-treated SHR-A3 from 2.62 to 2.0 (P=0.001). MMF treatment also reduced renal fibrosis in SHR-A3 (3.9 versus 2.0; P<0.001).
conclusionsPolygenic susceptibility to renal injury in hypertension arises in association with genetic variation in genes that participate in immune responses and is dramatically improved by reduction of immune system activity.
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