Myosin Light Chain Phosphatase Plays an Important Role in Cardiac Fibrosis in a Model of Mineralocorticoid Receptor-Associated Hypertension.
aldosterone
cardiac fibrosis
mineralocorticoid receptor
myosin light chain
phosphorylation
Journal
Journal of the American Heart Association
ISSN: 2047-9980
Titre abrégé: J Am Heart Assoc
Pays: England
ID NLM: 101580524
Informations de publication
Date de publication:
05 Mar 2024
05 Mar 2024
Historique:
medline:
11
3
2024
pubmed:
29
2
2024
entrez:
29
2
2024
Statut:
ppublish
Résumé
Myosin phosphatase targeting subunit 2 (MYPT2) is an important subunit of cardiac MLC (myosin light chain) phosphatase, which plays a crucial role in regulating the phosphorylation of MLC to phospho-MLC (p-MLC). A recent study demonstrated mineralocorticoid receptor-related hypertension is associated with RhoA/Rho-associated kinase/MYPT1 signaling upregulation in smooth muscle cells. Our purpose is to investigate the effect of MYPT2 on cardiac function and fibrosis in mineralocorticoid receptor-related hypertension. HL-1 murine cardiomyocytes were incubated with different concentrations or durations of aldosterone. After 24-hour stimulation, aldosterone increased CTGF (connective tissue growth factor) and MYPT2 and decreased p-MLC in a dose-dependent manner. MYPT2 knockdown decreased CTGF. Cardiac-specific MYPT2-knockout (c-MYPT2 Cardiac-specific MYPT2 knockout leads to decreased myosin light chain phosphatase and increased p-MLC. MYPT2 deletion prevented cardiac fibrosis and dysfunction in a model of mineralocorticoid receptor-associated hypertension.
Sections du résumé
BACKGROUND
BACKGROUND
Myosin phosphatase targeting subunit 2 (MYPT2) is an important subunit of cardiac MLC (myosin light chain) phosphatase, which plays a crucial role in regulating the phosphorylation of MLC to phospho-MLC (p-MLC). A recent study demonstrated mineralocorticoid receptor-related hypertension is associated with RhoA/Rho-associated kinase/MYPT1 signaling upregulation in smooth muscle cells. Our purpose is to investigate the effect of MYPT2 on cardiac function and fibrosis in mineralocorticoid receptor-related hypertension.
METHODS AND RESULTS
RESULTS
HL-1 murine cardiomyocytes were incubated with different concentrations or durations of aldosterone. After 24-hour stimulation, aldosterone increased CTGF (connective tissue growth factor) and MYPT2 and decreased p-MLC in a dose-dependent manner. MYPT2 knockdown decreased CTGF. Cardiac-specific MYPT2-knockout (c-MYPT2
CONCLUSIONS
CONCLUSIONS
Cardiac-specific MYPT2 knockout leads to decreased myosin light chain phosphatase and increased p-MLC. MYPT2 deletion prevented cardiac fibrosis and dysfunction in a model of mineralocorticoid receptor-associated hypertension.
Identifiants
pubmed: 38420846
doi: 10.1161/JAHA.123.032828
pmc: PMC10944028
doi:
Substances chimiques
Myosin-Light-Chain Phosphatase
EC 3.1.3.53
Receptors, Mineralocorticoid
0
Aldosterone
4964P6T9RB
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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