| First Author | Ye Z | Year | 2024 |
| Journal | J Am Heart Assoc | Volume | 13 |
| Issue | 5 | Pages | e032828 |
| PubMed ID | 38420846 | Mgi Jnum | J:366485 |
| Mgi Id | MGI:7613319 | Doi | 10.1161/JAHA.123.032828 |
| Citation | Ye Z, et al. (2024) Myosin Light Chain Phosphatase Plays an Important Role in Cardiac Fibrosis in a Model of Mineralocorticoid Receptor-Associated Hypertension. J Am Heart Assoc 13(5):e032828 |
| abstractText | 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: 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(-/-)) mice exhibited decreased type 1 phosphatase catalytic subunit beta and increased p-MLC. A disease model of mouse was induced by subcutaneous aldosterone and 8% NaCl food for 4 weeks after uninephrectomy. Blood pressure elevation and left ventricular hypertrophy were observed in both c-MYPT2(-/-) and MYPT2(+/+) mice, with no difference in heart weights or nuclear localization of mineralocorticoid receptor in cardiomyocytes. However, c-MYPT2(-/-) mice had higher ejection fraction and fractional shortening on echocardiography after aldosterone treatment. Histopathology revealed less fibrosis, reduced CTGF, and increased p-MLC in c-MYPT2(-/-) mice. Basal global radial strain and global longitudinal strain were higher in c-MYPT2(-/-) than in MYPT2(+/+) mice. After aldosterone treatment, both global radial strain and global longitudinal strain remained higher in c-MYPT2(-/-) mice compared with MYPT2(+/+) mice. 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. |
