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Global Translational Medicine Mineralocorticoid receptor in CMD

inhibition and MR antagonist . These data suggest that T and endothelial selectin [62,63] (Figure 3). Caprio et al. have
[56]
cell MR regulates the expression of chemokine receptors shown that aldosterone-activated MR increases ICAM-1
and inflammatory factors, affecting T cell aggregation and expression in primary human ECs and promotes leukocyte
the level of inflammation, respectively, thus affecting blood adhesion in vitro . Further experiments have shown that
[64]
pressure. ICAM-1 deletion in ECs alleviated vascular inflammation
and plaque areas in a mouse model of aldosterone-induced
2.3.2. Role of T cell MR in cardiac remodeling atherosclerosis and MR directly regulated the gene
[65]
The previous study has shown that T cell MR is also involved expression of ICAM-1 in ECs , suggesting that MR plays
in the pathological process of myocardial remodeling . a role in atherosclerosis disease through ICAM-1. Moss
[17]
In a mouse model of abdominal aortic contraction et al. have demonstrated that the deficiency of EC MR
(AAC)-induced cardiac hypertrophy, T cell MR deficiency did not affect the plaque size or composition in a mouse
reduces cardiac hypertrophy, fibrosis, inflammation, atherosclerosis model . However, plaque inflammation
[66]
and dysfunction . Consistently, MR antagonists inhibit was significantly ameliorated in EC MR knockout mice .
[66]
[57]
cardiac hypertrophy and fibrosis, induced by AAC, and These experimental results imply that EC MR mediates
reduce the accumulation and activation of CD4 and vascular inflammation in atherosclerosis.
+
CD8 T cells in mouse heart . Mechanistically, T cell MR
+
[57]
deletion could inhibit the expression of surface molecule 3.1.2. Role of endothelial cell MR in hypertension
CD44, CD69, and CD25, which are all important markers The role of vascular EC MR in blood pressure regulation
of T cell activation, suggesting that MR could directly has also been explored. Nguyen Dinh Cat et al. have
[57]
regulate T cell activation . Moreover, the deficiency of T demonstrated that the overexpression of MR in ECs elevates
cell MR suppresses the expression of IL-2 most likely by blood pressure at baseline and in response to endothelin
decreasing the amount of dephosphorylated NFATc2 . 1 or Ang II infusion as well as enhances the contractile
[57]
These results support that T cell MR contributes to cardiac response of mesenteric arteries to vasoconstrictors without
remodeling and dysfunction following pressure load. affecting the vascular morphology . In contrast, MR
[25]
deletion in ECs has no effect on blood pressure at baseline
2.4. B cell MR or in DOCA/salt- or Ang II-induced mouse models [67,68] .
B cells are adaptive immune cells, and their main functions However, EC MR deficiency has shown to ameliorate
include antibody generation, antigen presentation, T cell cardiac remodeling by inhibiting the recruitment of
co-stimulation, and cytokine production . B cells have macrophages and reducing the expression of myocardial
[58]
been progressively recognized as modulators of both pro-inflammatory factors in a mouse model of DOCA/salt-
adaptive and innate immune responses and for their role induced hypertension [67,68] . Meanwhile, EC MR deficiency
in the pathogenesis of CMDs, such as MI, HF, vascular has shown no effect on renal fibrosis, glomerular injury,
disease, and obesity-associated metabolic disease [58,59] . proteinuria, or inflammation in a DOCA/salt-induced
MR expression has been found in B cells . However, it is model [67-69] . Remarkably, MR deletion in ECs protects
[30]
still unclear whether B cell MR plays a role in CMDs and DOCA salt-induced aortic endothelial dysfunction but has
whether MR regulates B cell function. no effect on the mesenteric artery . In Ang II-induced
[68]
hypertension, EC MR deletion improves the dilatation
3. Vascular cell MR and CMDs function of mesenteric (but not coronary) artery .
[26]
3.1. Role of MR in endothelial cells These data suggest that EC MR is involved in regulating
vasoconstriction in a vascular bed-specific manner.
3.1.1. Role of endothelial cell MR in atherosclerosis
Atherosclerosis, a chronic inflammatory disease, is a 3.1.3. Role of endothelial cell MR in angiogenesis
risk factor for many other CVDs . Endothelial cells EC MR also plays a role in angiogenesis. Zheng et al.
[60]
(ECs) play an important role in the pathological process have demonstrated that the deletion of EC MR promotes
of atherosclerosis . In response to cardiovascular risk blood flow recovery and increases blood vessel density in
[61]
factors, injury to the vascular endothelium occurs, ischemic limbs in a mouse model of hindlimb ischemia .
[70]
and a dysfunctional endothelium in turn promotes the Moreover, MR knockout increases angiogenic potential,
adhesion and migration of white blood cells to vascular migration capacity, and EC proliferation in vitro .
[70]
walls . On the other hand, dysfunctional ECs promote Mechanistically, MR affects endothelial cell function by
[61]
vascular inflammation by expressing surface adhesion inhibiting signal transducer and activator of transcription
molecules, including intercellular adhesion molecule-1 3 (STAT3) expression by binding to CCAAT enhancer-
(ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), binding protein beta (C/EBPβ) (Figure 3). Interestingly,
[70]
Volume 2 Issue 1 (2023) 5 https://doi.org/10.36922/gtm.v2i1.229