Borges Celina Carvalho, Penna-de-Carvalho Aline, Medeiros Junior Jorge L, Aguila Marcia Barbosa, Mandarim-de-Lacerda Carlos A
Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Brazil.
Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Brazil.
Life Sci. 2017 Dec 15;191:1-8. doi: 10.1016/j.lfs.2017.10.002. Epub 2017 Oct 4.
The evaluation of the local Renin-Angiotensin-Aldosterone system (RAAS) gene expressions in the heart of ovariectomized (OVX) apolipoprotein E deficient mice (ApoE).
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.
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).
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.
评估去卵巢（OVX）载脂蛋白E缺陷小鼠（ApoE）心脏中局部肾素-血管紧张素-醛固酮系统（RAAS）基因的表达。
将4月龄C57BL/6雌性小鼠（野生型，wt，n = 20）和ApoE雌性小鼠（n = 20）进行去卵巢手术或不切除卵巢的手术（假手术，SHAM），形成四组（每组n = 10）：假手术/wt、假手术/ApoE、去卵巢/wt和去卵巢/ApoE。
去卵巢导致体重增加、血浆甘油三酯（TG）和总胆固醇升高，导致胰岛素抵抗，并改变心脏组织中RAAS基因的表达。去卵巢/wt组中血管紧张素转换酶（ACE）-2的基因表达低于假手术/wt组（P = 0.0004），Mas受体（MASr）低于假手术/wt组（P < 0.0001）。此外，去卵巢/wt组中血管紧张素II 1型受体（AT1r）高于假手术/wt组（P = 0.0229），而血管紧张素II 2型受体（AT2r）低于假手术/wt组（P = 0.0121）。去卵巢和ApoE缺陷显示出相互作用，加剧胰岛素抵抗，增加TG水平并改变ACE和MASr基因表达。去卵巢/ApoE组中ACE基因表达高于去卵巢/wt组（P < 0.0001），而MASr基因表达低于去卵巢/wt组（P < 0.0001）。
去卵巢对ApoE缺陷动物心脏中局部RAAS级联反应的影响，除了导致胰岛素抵抗的代谢变化外，还涉及肾素、ACE和AT1r基因表达的上调。这些发现可能有助于阐明绝经后高血压的发病机制以及RAAS与载脂蛋白E之间的联系。
