Differential Expression of Hypertensive Phenotypes in BXD Mouse Strains in Response to Angiotensin II

Wenyuan Zhao, Tieqiang Zhao, Yuanjian Chen, Syamal Bhattacharya, Lu Lu, Yao Sun

Research output: Contribution to journalArticle

Abstract

BACKGROUND Besides environmental risk factors, genetic factors play a crucial role in the pathogenesis of primary hypertension. The current study is to unravel whether hypertensive phenotypes vary in mice with different genetic background. METHODS Hypertension was induced in C57BL/6J (B6), DBA/2J (D2), and 25 BXD strains by administrating angiotensin (Ang)II (2.5 mg/kg/day infused by osmotic minipump) for 4 weeks. Systolic blood pressure was monitored before (baseline) and after 4 weeks of AngII treatment by tail cuff. Cardiac and renal fibrosis was evaluated by picrosirius red staining and collagen volume fraction (CVF) was quantitated using imaging analyzing system; cardiac transforming growth factor (TGF)-β gene expression was monitored by RT-PCR, and inflammatory response was detected by immunohistochemical ED-1 staining. RESULTS AngII infusion caused hypertension in all strains. However, blood pressure elevation was more evident in the D2 strain than the B6 group, while it was widely variable among BXD strains. Furthermore, chronic AngII treatment lead to development of hypertensive cardiac and renal diseases. Cardiac and renal CVF levels in the D2 strain was significantly higher than the B6 cohort, whereas these varied vastly across BXD strains. Moreover, cardiac TGF-β mRNA levels were markedly diverse among various mouse strains. CONCLUSION Our study unequivocally demonstrates that in response to AngII, BXDs with different genetic background expressed hypertension phenotypes with varied degree in severity. It implicates that genomics contribute to pathogenesis of primary hypertension. Building upon the genotype and hypertensive phenotypes, the BXD cohort can be further exploited experimentally to identify genes that influence blood pressure.

Original languageEnglish (US)
Pages (from-to)108-114
Number of pages7
JournalAmerican journal of hypertension
Volume31
Issue number1
DOIs
StatePublished - Jan 1 2018

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Angiotensin II
Hypertension
Phenotype
Blood Pressure
Transforming Growth Factors
Kidney
Collagen
Staining and Labeling
Genomics
Tail
Heart Diseases
Fibrosis
Genotype
Gene Expression
Polymerase Chain Reaction
Messenger RNA
Genes
Genetic Background

All Science Journal Classification (ASJC) codes

  • Internal Medicine

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Differential Expression of Hypertensive Phenotypes in BXD Mouse Strains in Response to Angiotensin II. / Zhao, Wenyuan; Zhao, Tieqiang; Chen, Yuanjian; Bhattacharya, Syamal; Lu, Lu; Sun, Yao.

In: American journal of hypertension, Vol. 31, No. 1, 01.01.2018, p. 108-114.

Research output: Contribution to journalArticle

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