Ovariectomy modify local renin-angiotensin-aldosterone system gene expressions in the heart of ApoE (−/−) mice

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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.

Graphical abstract

There is upregulation of the renin-angiotensin-aldosterone system in the heart of ovariectomized apolipoprotein deficient mouse, characterized by the enhancement of the renin, angiotensin 2 receptor type 1 (AT1r) and the angiotensin-converting enzyme (ACE). On the contrary, there is downregulation of AT2r, ACE2 and MAS receptor in the heart of these animals.

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