IMR Press / FBL / Volume 13 / Issue 13 / DOI: 10.2741/3071

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article

Genetic background in apolipoprotein A-I and cystathionine β-synthase deficiency

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1 Departamento de Bioquimica y Biologia Molecular y Celular, Facultad de Veterinaria, Universidad de Zaragoza, Spain
2 Departamento de Patologia Animal, Facultad de Veterinaria, Universidad de Zaragoza, Spain
3 Departamento de Toxicologia, Facultad de Veterinaria, Universidad de Zaragoza, Spain
4 CIBER de Fisiopatologia de la Obesidad y Nutricion, Instituto de Salud Carlos III, Spain

*Author to whom correspondence should be addressed.

Front. Biosci. (Landmark Ed) 2008, 13(13), 5155–5162; https://doi.org/10.2741/3071
Published: 1 May 2008
Abstract

Double heterozygous mice lacking one allele of Cbs and Apoa1 develop hyperhomocysteinemia and hypoalphalipoproteinemia together with moderate hypertension. To study the influence of the genetic background into this specific phenotype, four groups of male mice were established: control and double heterozygous groups in C57BL/6J and in C57BL/6J x 129 backgrounds, respectively. Nitric oxide levels, systolic blood pressure, plasma lipid parameters, arylesterase activity and aorta histology were analyzed as well as oligonucleotide array hybridization of liver RNA. Results demonstrated that double heterozygous mice in C57BL/6J substrate had a milder phenotype showing lower increase in blood pressure compared to double heterozygous group in hybrid background. The severity of the phenotype in the latter group was associated with lower nitric oxide and arylesterase activity levels, and hyperplasia of the vascular media layer. Hepatic profiling of both genetic substrates showed profound differences in expression of contractile proteins that could explain these pathological findings. In summary, the phenotypic presentation of hypertension is associated with multiple processes from vascular bedside to liver as evidenced by nitric oxide production or paraoxonase levels.

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