3A.03. Blood-pressure associated variants in NPR3 affect human vascular smooth muscle cells proliferation and calcium response to angiotensin II

Introduction: A recent genome-wide association study identified a locus within natriuretic peptide receptor C (NPR3) to be significantly associated with blood pressure (BP). (1) Objective: To functionally characterise the effect of BP- associated SNPs (single nucleotide polymorphisms) at the NPR3 lo...

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Bibliographic Details
Published in:Journal of human hypertension 2015-10, Vol.29 (10), p.624
Main Authors: Ren, Meixia, Ng, Fu Liang, Witkowska, Kate, Baron, Michael, Townsend-Nicholson, Andrea, Xiao, Qingzhong, Hobbs, Adrian, Ye, Shu, Caulfield, Mark
Format: Article
Language:English
Subjects:
Angiotensins
Blood pressure
Genetic aspects
Natriuretic peptides
Physiological aspects
Single nucleotide polymorphisms
Smooth muscle
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Summary:Introduction: A recent genome-wide association study identified a locus within natriuretic peptide receptor C (NPR3) to be significantly associated with blood pressure (BP). (1) Objective: To functionally characterise the effect of BP- associated SNPs (single nucleotide polymorphisms) at the NPR3 locus in the context of BP regulatory pathways. Methods: Primary human umbilical smooth muscle (HUASMCs) and endothelial (HUVECs) cells of different NPR3 genotypes were investigated. Genotype-specific mRNA and protein expression were assessed by qRT-PCR and western blotting. Open chromatin regions were assayed using formaldehyde-assisted isolation of regulatory elements (FAIRE). Cell proliferation and migration were detected by cell counting and scratch assays. Angiotensin II (AngII)-induced [Ca.sup.2+] flux was detected using an intracellular fluorescent probe (calcium 6). Results: The NPR3 risk allele (major allele) in HUASMCs was associated with lower endogenous mRNA (P
ISSN:0950-9240
DOI:10.1038/jhh.2015.90