Deoxycorticosterone Acetate/Salt-Induced Cardiac But Not Renal Injury Is Mediated By Endothelial Mineralocorticoid Receptors Independently From Blood Pressure
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Deoxycorticosterone Acetate/Salt-Induced Cardiac But Not Renal Injury Is Mediated By Endothelial Mineralocorticoid Receptors Independently From Blood Pressure. / Lother, Achim; Fürst, David; Bergemann, Stella; Gilsbach, Ralf; Grahammer, Florian; Huber, Tobias B; Hilgendorf, Ingo; Bode, Christoph; Moser, Martin; Hein, Lutz.
in: HYPERTENSION, Jahrgang 67, Nr. 1, 01.2016, S. 130-8.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Deoxycorticosterone Acetate/Salt-Induced Cardiac But Not Renal Injury Is Mediated By Endothelial Mineralocorticoid Receptors Independently From Blood Pressure
AU - Lother, Achim
AU - Fürst, David
AU - Bergemann, Stella
AU - Gilsbach, Ralf
AU - Grahammer, Florian
AU - Huber, Tobias B
AU - Hilgendorf, Ingo
AU - Bode, Christoph
AU - Moser, Martin
AU - Hein, Lutz
N1 - © 2015 American Heart Association, Inc.
PY - 2016/1
Y1 - 2016/1
N2 - Chronic kidney disease has a tremendously increasing prevalence and requires novel therapeutic approaches. Mineralocorticoid receptor (MR) antagonists have proven highly beneficial in the therapy of cardiac disease. The cellular and molecular events leading to cardiac inflammation and remodeling are proposed to be similar to those mediating renal injury. Thus, this study was designed to evaluate and directly compare the effect of MR deletion in endothelial cells on cardiac and renal injury in a model of deoxycorticosterone acetate-induced hypertension. Endothelial MR deletion ameliorated deoxycorticosterone acetate/salt-induced cardiac remodeling. This was associated with a reduced expression of the vascular cell adhesion molecule Vcam1 in MR-deficient cardiac endothelial cells. Ambulatory blood pressure telemetry revealed that the protective effect of MR deletion was independent from blood pressure. Similar to the heart, deoxycorticosterone acetate/salt-induced severe renal injury, including inflammation, fibrosis, glomerular injury, and proteinuria. However, no differences in renal injury were observed between genotypes. In conclusion, MR deletion from endothelial cells ameliorated deoxycorticosterone acetate/salt-induced cardiac inflammation and remodeling independently from alterations in blood pressure but it did not affect renal injury. These findings suggest that the anti-inflammatory mechanism mediating organ protection after endothelial cell MR deletion is specific for the heart versus the kidney.
AB - Chronic kidney disease has a tremendously increasing prevalence and requires novel therapeutic approaches. Mineralocorticoid receptor (MR) antagonists have proven highly beneficial in the therapy of cardiac disease. The cellular and molecular events leading to cardiac inflammation and remodeling are proposed to be similar to those mediating renal injury. Thus, this study was designed to evaluate and directly compare the effect of MR deletion in endothelial cells on cardiac and renal injury in a model of deoxycorticosterone acetate-induced hypertension. Endothelial MR deletion ameliorated deoxycorticosterone acetate/salt-induced cardiac remodeling. This was associated with a reduced expression of the vascular cell adhesion molecule Vcam1 in MR-deficient cardiac endothelial cells. Ambulatory blood pressure telemetry revealed that the protective effect of MR deletion was independent from blood pressure. Similar to the heart, deoxycorticosterone acetate/salt-induced severe renal injury, including inflammation, fibrosis, glomerular injury, and proteinuria. However, no differences in renal injury were observed between genotypes. In conclusion, MR deletion from endothelial cells ameliorated deoxycorticosterone acetate/salt-induced cardiac inflammation and remodeling independently from alterations in blood pressure but it did not affect renal injury. These findings suggest that the anti-inflammatory mechanism mediating organ protection after endothelial cell MR deletion is specific for the heart versus the kidney.
KW - Animals
KW - Blood Pressure
KW - Cells, Cultured
KW - Desoxycorticosterone Acetate
KW - Disease Models, Animal
KW - Endothelium, Vascular
KW - Gene Expression Regulation
KW - Hypertension
KW - Immunohistochemistry
KW - Kidney
KW - Male
KW - Mice
KW - Mice, Mutant Strains
KW - Polymerase Chain Reaction
KW - RNA
KW - Receptors, Mineralocorticoid
KW - Vascular Cell Adhesion Molecule-1
KW - Ventricular Remodeling
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1161/HYPERTENSIONAHA.115.06530
DO - 10.1161/HYPERTENSIONAHA.115.06530
M3 - SCORING: Journal article
C2 - 26553231
VL - 67
SP - 130
EP - 138
JO - HYPERTENSION
JF - HYPERTENSION
SN - 0194-911X
IS - 1
ER -