Endothelial cell mineralocorticoid receptors regulate deoxycorticosterone/salt-mediated cardiac remodeling and vascular reactivity but not blood pressure
Recent studies have identified novel pathological roles for mineralocorticoid receptors (MR) in specific cell types in cardiovascular disease. The mechanisms by which MR promotes inflammation and fibrosis involve multiple cell-specific events. To identify the role of MR in endothelial cells (EC-MR), the current study explored the vascular responses to aldosterone in wild-type (WT) and EC-null mice (EC-MRKO). Nitric oxide function was impaired in the thoracic aorta and mesenteric arteries of aldosterone-treated WT mice. Although endothelial nitric oxide function was equivalently impaired in the mesenteric arteries of aldosterone-treated EC-MRKO mice, endothelial function was unaffected in the aorta, suggesting a differential role for EC-MR depending on the vascular bed. Second, the contribution of EC-MR to cardiovascular inflammation, fibrosis, and hypertension was determined in WT and EC-MRKO treated with deoxycorticosterone/salt for 8 days or 8 weeks. At 8 days, loss of EC-MR prevented macrophage infiltration and the expression of proinflammatory genes in the myocardium. Increased cardiac fibrosis was not detected in either genotype at this time, mRNA levels of profibrotic genes were significantly lower in EC-MRKO mice versus WT. At 8 weeks, deoxycorticosterone/salt treatment increased macrophage recruitment and proinflammatory gene expression in WT but not in EC-MRKO. Collagen deposition and connective tissue growth factor expression were significantly reduced in EC-MRKO versus WT. Interestingly, systolic blood pressure was equivalently elevated in deoxycorticosterone/salt treated WT and EC-MRKO. Our data demonstrate that (1) EC-MR signaling contributes to vascular nitric oxide function in large conduit arteries but not in resistance vessels and (2) an independent role for EC-MR in the inflammatory and profibrotic response to deoxycorticosterone/salt.
| Errataetall: |
CommentIn: Hypertension. 2014 May;63(5):915-7. - PMID 24566083 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2014 |
|---|---|
| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:63 |
|---|---|
| Enthalten in: |
Hypertension (Dallas, Tex. : 1979) - 63(2014), 5 vom: 24. Mai, Seite 1033-40 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Rickard, Amanda J [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 11.09.2014 Date Revised 23.10.2019 published: Print-Electronic CommentIn: Hypertension. 2014 May;63(5):915-7. - PMID 24566083 Citation Status MEDLINE |
|---|
| doi: |
10.1161/HYPERTENSIONAHA.113.01803 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM235818488 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM235818488 | ||
| 003 | DE-627 | ||
| 005 | 20231224104219.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2014 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1161/HYPERTENSIONAHA.113.01803 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0786.xml |
| 035 | |a (DE-627)NLM235818488 | ||
| 035 | |a (NLM)24566081 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Rickard, Amanda J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Endothelial cell mineralocorticoid receptors regulate deoxycorticosterone/salt-mediated cardiac remodeling and vascular reactivity but not blood pressure |
| 264 | 1 | |c 2014 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 11.09.2014 | ||
| 500 | |a Date Revised 23.10.2019 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Hypertension. 2014 May;63(5):915-7. - PMID 24566083 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Recent studies have identified novel pathological roles for mineralocorticoid receptors (MR) in specific cell types in cardiovascular disease. The mechanisms by which MR promotes inflammation and fibrosis involve multiple cell-specific events. To identify the role of MR in endothelial cells (EC-MR), the current study explored the vascular responses to aldosterone in wild-type (WT) and EC-null mice (EC-MRKO). Nitric oxide function was impaired in the thoracic aorta and mesenteric arteries of aldosterone-treated WT mice. Although endothelial nitric oxide function was equivalently impaired in the mesenteric arteries of aldosterone-treated EC-MRKO mice, endothelial function was unaffected in the aorta, suggesting a differential role for EC-MR depending on the vascular bed. Second, the contribution of EC-MR to cardiovascular inflammation, fibrosis, and hypertension was determined in WT and EC-MRKO treated with deoxycorticosterone/salt for 8 days or 8 weeks. At 8 days, loss of EC-MR prevented macrophage infiltration and the expression of proinflammatory genes in the myocardium. Increased cardiac fibrosis was not detected in either genotype at this time, mRNA levels of profibrotic genes were significantly lower in EC-MRKO mice versus WT. At 8 weeks, deoxycorticosterone/salt treatment increased macrophage recruitment and proinflammatory gene expression in WT but not in EC-MRKO. Collagen deposition and connective tissue growth factor expression were significantly reduced in EC-MRKO versus WT. Interestingly, systolic blood pressure was equivalently elevated in deoxycorticosterone/salt treated WT and EC-MRKO. Our data demonstrate that (1) EC-MR signaling contributes to vascular nitric oxide function in large conduit arteries but not in resistance vessels and (2) an independent role for EC-MR in the inflammatory and profibrotic response to deoxycorticosterone/salt | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a deoxycorticosterone | |
| 650 | 4 | |a endothelial cells | |
| 650 | 4 | |a macrophages | |
| 650 | 4 | |a receptors, mineralocorticoid | |
| 650 | 7 | |a CCN2 protein, human |2 NLM | |
| 650 | 7 | |a Receptors, Mineralocorticoid |2 NLM | |
| 650 | 7 | |a Intercellular Adhesion Molecule-1 |2 NLM | |
| 650 | 7 | |a 126547-89-5 |2 NLM | |
| 650 | 7 | |a Connective Tissue Growth Factor |2 NLM | |
| 650 | 7 | |a 139568-91-5 |2 NLM | |
| 650 | 7 | |a Desoxycorticosterone |2 NLM | |
| 650 | 7 | |a 40GP35YQ49 |2 NLM | |
| 650 | 7 | |a Sodium Chloride |2 NLM | |
| 650 | 7 | |a 451W47IQ8X |2 NLM | |
| 650 | 7 | |a Aldosterone |2 NLM | |
| 650 | 7 | |a 4964P6T9RB |2 NLM | |
| 700 | 1 | |a Morgan, James |e verfasserin |4 aut | |
| 700 | 1 | |a Chrissobolis, Sophocles |e verfasserin |4 aut | |
| 700 | 1 | |a Miller, Alyson A |e verfasserin |4 aut | |
| 700 | 1 | |a Sobey, Christopher G |e verfasserin |4 aut | |
| 700 | 1 | |a Young, Morag J |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Hypertension (Dallas, Tex. : 1979) |d 1983 |g 63(2014), 5 vom: 24. Mai, Seite 1033-40 |w (DE-627)NLM000456136 |x 1524-4563 |7 nnns |
| 773 | 1 | 8 | |g volume:63 |g year:2014 |g number:5 |g day:24 |g month:05 |g pages:1033-40 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1161/HYPERTENSIONAHA.113.01803 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 63 |j 2014 |e 5 |b 24 |c 05 |h 1033-40 | ||