2001
DOI: 10.1074/jbc.m103984200
|View full text |Cite
|
Sign up to set email alerts
|

Alteration of Cardiac and Renal Functions in Transgenic Mice Overexpressing Human Mineralocorticoid Receptor

Abstract: The mineralocorticoid receptor (MR), a ligand-dependent transcription factor, mediates aldosterone actions in a large variety of tissues. To explore the functional implication of MR in pathophysiology, transgenic mouse models were generated using the proximal human MR (hMR) promoter to drive expression of hMR in aldosterone target tissues. Tissue-specific analysis of transgene expression in two independent transgenic animal (TG) lines by ribonuclease protection assays revealed that hMR is expressed in all mine… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

5
68
0

Year Published

2002
2002
2017
2017

Publication Types

Select...
5
2
1

Relationship

0
8

Authors

Journals

citations
Cited by 110 publications
(73 citation statements)
references
References 35 publications
5
68
0
Order By: Relevance
“…While overexpression of MR in cardiomyocytes induces spontaneous development of classical features of HF such as cardiac hypertrophy and fibrosis (Le Menuet et al. 2001; Ouvrard‐Pascaud et al. 2005), cell‐specific deletion of MR has provided divergent results depending on the cell targeted and the HF model used.…”
Section: Discussionmentioning
confidence: 99%
“…While overexpression of MR in cardiomyocytes induces spontaneous development of classical features of HF such as cardiac hypertrophy and fibrosis (Le Menuet et al. 2001; Ouvrard‐Pascaud et al. 2005), cell‐specific deletion of MR has provided divergent results depending on the cell targeted and the HF model used.…”
Section: Discussionmentioning
confidence: 99%
“…Moreover, inflammatory cells were present in the cardiac fibrosis obtained after experimental hyperaldosteronism (15), which is not the case here. Transgenic mice with overexpression of human MR in heart and kidney exhibit mild cardiopathy without cardiac fibrosis (29). These observations raise further questions about the role of the cardiac MR in the aldosteronesalt model.…”
Section: Down-expression Of Endogenous Mr Mrna Leads To Cardiac Remod-mentioning
confidence: 89%
“…A targeted approach, as used in this study, is critical to determine the role of the transgene in heart independent of its function in other cell types. This model allows analysis of the specific contribution of MR in heart, and therefore differs from previous models, in which MR expression has been altered constitutively in multiple organs by overexpression (29) or gene inactivation (10), leading to both local and systemic effects. Here we observe that decreased cardiac MR without hyperaldosteronism dramatically affects cardiac structure and function in mice, leading to cardiac hypertrophy, ventricular dysfunction, interstitial fibrosis, and heart failure.…”
Section: Heart Failure and Cardiac Remodeling Are Reversible When Mmrmentioning
confidence: 97%
“…To examine the possible involvement of Ang II or other active products of the renin-angiotensin system, such as Ang [1][2][3][4][5][6][7] , in cardiac aldosterone synthesis through receptors other than AT 1A , we examined the effects of lisinopril, an ACE inhibitor. As shown in Figure 5A, treatment with lisinopril (20 mg/kg per day) significantly attenuated LV hypertrophy observed in WT mice but did not further reduce LV weight in AT 1A -KO MI mice.…”
Section: Mechanism Underlying Renin-angiotensin System-independent Almentioning
confidence: 99%
“…5,6 Although one of the primary targets of aldosterone is the kidney, there is also evidence that aldosterone directly affects cardiac tissues and causes the development of cardiac hypertrophy, fibrosis, and heart failure. 7,8 Accumulating evidence suggests production of aldosterone in cardiac tissues, particularly under pathological conditions. Aldosterone synthase (CYP11B2) is detected in the hearts of several species, including rats 9,10 and humans.…”
mentioning
confidence: 99%