Key result
Deletion of the mineralocorticoid receptor in myeloid cells protected female mice against Angiotensin II-induced aortic endothelial stiffening and vasorelaxation dysfunction.
Why the study?
There is a lack of knowledge regarding the role of mineralocorticoid receptor-induced adipose tissue inflammation in the genesis of vascular dysfunction in women.
Does mineralocorticoid receptor deletion in myeloid cells prevent Angiotensin II-induced aortic stiffening and endothelial dysfunction in female mice?
Does mineralocorticoid receptor deletion in myeloid cells prevent Angiotensin II-induced aortic stiffening and endothelial dysfunction in female mice?
Deletion of mineralocorticoid receptors in myeloid cells protects female mice from Angiotensin II-induced vascular dysfunction and adipose tissue inflammation, highlighting a potential mechanism and therapeutic target for cardiovascular disease in women.
Caution against clinical translation in women; hypothesis-generating for myeloid MR as sex-specific target.
Enhanced mineralocorticoid receptor (MR) signaling is critical to the development of endothelial dysfunction and arterial stiffening. However, there is a lack of knowledge about the role of MR-induced adipose tissue inflammation in the genesis of vascular dysfunction in women. In this study, we hypothesize that MR activation in myeloid cells contributes to angiotensin II (Ang II)-induced aortic stiffening and endothelial dysfunction in females via increased pro-inflammatory (M1) macrophage polarization. Female mice lacking MR in myeloid cells (MyMRKO) were infused with Ang II (500 ng/kg/min) for 4 weeks. This was followed by determinations of aortic stiffness and vasomotor responses, as well as measurements of markers of inflammation and macrophage infiltration/polarization in different adipose tissue compartments. MyMRKO mice were protected against Ang II-induced aortic endothelial stiffening, as assessed via atomic force microscopy in aortic explants, and vasorelaxation dysfunction, as measured by aortic wire myography. In alignment, MyMRKO mice were protected against Ang II-induced macrophage infiltration and M1 polarization in visceral adipose tissue (VAT) and thoracic perivascular adipose tissue (tPVAT). Collectively, this study demonstrates a critical role of MR activation in myeloid cells in the pathogenesis of vascular dysfunction in females associated with pro-inflammatory macrophage polarization in VAT and tPVAT. Our data have potential clinical implications for the prevention and management of cardiovascular disease in women, who are disproportionally at higher risk for poor outcomes.
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Manrique‐Acevedo et al. (2021) studied Angiotensin II-induced vascular dysfunction. Myeloid mineralocorticoid receptor deletion vs. Littermate controls (MR intact) was evaluated on Aortic endothelial stiffness and vasorelaxation dysfunction (p=≤0.05). Deletion of the mineralocorticoid receptor in myeloid cells protected female mice against Angiotensin II-induced aortic endothelial stiffening and vasorelaxation dysfunction.
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