Cardiomyocyte Mineralocorticoid Receptor Activation Impairs Acute Cardiac Functional Recovery After Ischemic Insult
© 2015 American Heart Association, Inc..
Loss of mineralocorticoid receptor signaling selectively in cardiomyocytes can ameliorate cardiac fibrotic and inflammatory responses caused by excess mineralocorticoids. The aim of this study was to characterize the role of cardiomyocyte mineralocorticoid receptor signaling in ischemia-reperfusion injury and recovery and to identify a role of mineralocorticoid receptor modulation of cardiac function. Wild-type and cardiomyocyte mineralocorticoid receptor knockout mice (8 weeks) were uninephrectomized and maintained on (1) high salt (0.9% NaCl, 0.4% KCl) or (2) high salt plus deoxycorticosterone pellet (0.3 mg/d, 0.9% NaCl, 0.4% KCl). After 8 weeks of treatment, hearts were isolated and subjected to 20 minutes of global ischemia plus 45 minutes of reperfusion. Mineralocorticoid excess increased peak contracture during ischemia regardless of genotype. Recovery of left ventricular developed pressure and rates of contraction and relaxation post ischemia-reperfusion were greater in knockout versus wild-type hearts. The incidence of arrhythmic activity during early reperfusion was significantly higher in wild-type than in knockout hearts. Levels of autophosphorylated Ca(2+)/calmodulin protein kinase II (Thr287) were elevated in hearts from wild-type versus knockout mice and associated with increased sodium hydrogen exchanger-1 expression. These findings demonstrate that cardiomyocyte-specific mineralocorticoid receptor-dependent signaling contributes to electromechanical vulnerability in acute ischemia-reperfusion via a mechanism involving Ca(2+)/calmodulin protein kinase II activation in association with upstream alteration in expression regulation of the sodium hydrogen exchanger-1.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2015 |
|---|---|
| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:66 |
|---|---|
| Enthalten in: |
Hypertension (Dallas, Tex. : 1979) - 66(2015), 5 vom: 21. Nov., Seite 970-7 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Bienvenu, Laura A [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 11.02.2016 Date Revised 16.11.2017 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1161/HYPERTENSIONAHA.115.05981 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM252569881 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM252569881 | ||
| 003 | DE-627 | ||
| 005 | 20231224164404.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2015 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1161/HYPERTENSIONAHA.115.05981 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0841.xml |
| 035 | |a (DE-627)NLM252569881 | ||
| 035 | |a (NLM)26351032 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Bienvenu, Laura A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cardiomyocyte Mineralocorticoid Receptor Activation Impairs Acute Cardiac Functional Recovery After Ischemic Insult |
| 264 | 1 | |c 2015 | |
| 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 11.02.2016 | ||
| 500 | |a Date Revised 16.11.2017 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2015 American Heart Association, Inc. | ||
| 520 | |a Loss of mineralocorticoid receptor signaling selectively in cardiomyocytes can ameliorate cardiac fibrotic and inflammatory responses caused by excess mineralocorticoids. The aim of this study was to characterize the role of cardiomyocyte mineralocorticoid receptor signaling in ischemia-reperfusion injury and recovery and to identify a role of mineralocorticoid receptor modulation of cardiac function. Wild-type and cardiomyocyte mineralocorticoid receptor knockout mice (8 weeks) were uninephrectomized and maintained on (1) high salt (0.9% NaCl, 0.4% KCl) or (2) high salt plus deoxycorticosterone pellet (0.3 mg/d, 0.9% NaCl, 0.4% KCl). After 8 weeks of treatment, hearts were isolated and subjected to 20 minutes of global ischemia plus 45 minutes of reperfusion. Mineralocorticoid excess increased peak contracture during ischemia regardless of genotype. Recovery of left ventricular developed pressure and rates of contraction and relaxation post ischemia-reperfusion were greater in knockout versus wild-type hearts. The incidence of arrhythmic activity during early reperfusion was significantly higher in wild-type than in knockout hearts. Levels of autophosphorylated Ca(2+)/calmodulin protein kinase II (Thr287) were elevated in hearts from wild-type versus knockout mice and associated with increased sodium hydrogen exchanger-1 expression. These findings demonstrate that cardiomyocyte-specific mineralocorticoid receptor-dependent signaling contributes to electromechanical vulnerability in acute ischemia-reperfusion via a mechanism involving Ca(2+)/calmodulin protein kinase II activation in association with upstream alteration in expression regulation of the sodium hydrogen exchanger-1 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a deoxycorticosterone | |
| 650 | 4 | |a ischemia | |
| 650 | 4 | |a mineralocorticoids | |
| 650 | 4 | |a myocyte, cardiac | |
| 650 | 4 | |a receptors, mineralocorticoid | |
| 650 | 4 | |a reperfusion | |
| 650 | 7 | |a Receptors, Estrogen |2 NLM | |
| 650 | 7 | |a Receptors, Mineralocorticoid |2 NLM | |
| 650 | 7 | |a Sodium-Hydrogen Exchangers |2 NLM | |
| 650 | 7 | |a Calcium-Calmodulin-Dependent Protein Kinase Type 2 |2 NLM | |
| 650 | 7 | |a EC 2.7.11.17 |2 NLM | |
| 650 | 7 | |a Calcium |2 NLM | |
| 650 | 7 | |a SY7Q814VUP |2 NLM | |
| 700 | 1 | |a Reichelt, Melissa E |e verfasserin |4 aut | |
| 700 | 1 | |a Morgan, James |e verfasserin |4 aut | |
| 700 | 1 | |a Fletcher, Elizabeth K |e verfasserin |4 aut | |
| 700 | 1 | |a Bell, James R |e verfasserin |4 aut | |
| 700 | 1 | |a Rickard, Amanda J |e verfasserin |4 aut | |
| 700 | 1 | |a Delbridge, Lea M |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 66(2015), 5 vom: 21. Nov., Seite 970-7 |w (DE-627)NLM000456136 |x 1524-4563 |7 nnns |
| 773 | 1 | 8 | |g volume:66 |g year:2015 |g number:5 |g day:21 |g month:11 |g pages:970-7 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1161/HYPERTENSIONAHA.115.05981 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 66 |j 2015 |e 5 |b 21 |c 11 |h 970-7 | ||