ABSTRACT
AIMS: The evaluation of the local Renin-Angiotensin-Aldosterone system (RAAS) gene expressions in the heart of ovariectomized (OVX) apolipoprotein E deficient mice (ApoE). METHODS: Four-months old C57BL/6 female mice (wild-type, wt, n=20), and ApoE female mice (n=20), were submitted to OVX or a surgical procedure without ovary removal (SHAM) and formed four groups (n=10/group): SHAM/wt, SHAM/ApoE, OVX/wt, and OVX/ApoE. KEY FINDINGS: OVX led to greater body mass, plasma triglycerides (TG) and total cholesterol, and resulted in insulin resistance and altered RAAS gene expressions in the heart tissue. The gene expression of angiotensin-converting enzyme (ACE)-2 was lower in OVX/wt than in SHAM/wt (P=0.0004), Mas receptor (MASr) was lower in OVX/wt compared to SHAM/wt (P<0.0001). Also, angiotensin II receptor type 1 (AT1r) was higher in OVX/wt than in SHAM/wt (P=0.0229), and AT2r was lower in OVX/wt than in SHAM/wt (P=0.0121). OVX and ApoE deficiency showed interaction potentializing the insulin resistance, increasing TG levels and altering ACE and MASr gene expressions. ACE gene expression was higher in OVX/ApoE than in OVX/wt (P<0.0001), and MASr gene expression was lower in OVX/ApoE than in OVX/wt (P<0.0001). SIGNIFICANCE: The impact of OVX on local RAAS cascade in the heart of ApoE deficient animals, besides the metabolic changes culminating with insulin resistance, involves an upregulation of renin, ACE, and AT1r gene expressions. The findings may contribute to clarify the mechanisms of development of postmenopausal hypertension and the link between RAAS and apolipoprotein E.
Subject(s)
Apolipoproteins E/genetics , Gene Expression Regulation , Myocardium/metabolism , Renin-Angiotensin System , Adaptor Proteins, Signal Transducing/genetics , Angiotensin-Converting Enzyme 2 , Animals , Female , Gene Deletion , Hypertension/etiology , Hypertension/genetics , Hypertension/metabolism , Insulin Resistance , Mice, Inbred C57BL , Mice, Knockout , Ovariectomy , Peptidyl-Dipeptidase A/genetics , Postmenopause , Renin/geneticsABSTRACT
Uno de los avances biotecnológicos más importantes de las últimas décadas fue el desarrollo de los animales transgénicos. En este artículo seanaliza por qué los animales transgénicos son excelentes modelos para estudiar la función y regulación de los genes y para buscar nuevas estrategias terapéuticas para las enfermedades humanas. Se discute su uso como biorreactores para producir productos farmacológicos para el tratamiento de enfermedades y la posibilidad de generar cerdos transgénicos como fuente alternativa a la donación de órganos.(AU)
One of the most important advances in biotechnology during the last decades was the development of transgenic animals. In this article, I discuss why transgenic animals are excellentmodels to analyze gen function and regulation, and to look for new therapeutic strategies for human diseases. Moreover, their use as bioreactors to produce pharmaceutical products for the treatment of human diseases, and the possibility of generating transgenic pigs as analternative source of organ donors for humans is also discussed.(AU)
Subject(s)
Animals , Animals, Genetically Modified , Bioreactors , Transplantation, Heterologous/adverse effects , Transplantation, Heterologous/statistics & numerical dataABSTRACT
Uno de los avances biotecnológicos más importantes de las últimas décadas fue el desarrollo de los animales transgénicos. En este artículo seanaliza por qué los animales transgénicos son excelentes modelos para estudiar la función y regulación de los genes y para buscar nuevas estrategias terapéuticas para las enfermedades humanas. Se discute su uso como biorreactores para producir productos farmacológicos para el tratamiento de enfermedades y la posibilidad de generar cerdos transgénicos como fuente alternativa a la donación de órganos.
One of the most important advances in biotechnology during the last decades was the development of transgenic animals. In this article, I discuss why transgenic animals are excellentmodels to analyze gen function and regulation, and to look for new therapeutic strategies for human diseases. Moreover, their use as bioreactors to produce pharmaceutical products for the treatment of human diseases, and the possibility of generating transgenic pigs as analternative source of organ donors for humans is also discussed.