| First Author | Rios FJ | Year | 2022 |
| Journal | Commun Biol | Volume | 5 |
| Issue | 1 | Pages | 746 |
| PubMed ID | 35882956 | Mgi Jnum | J:342306 |
| Mgi Id | MGI:7325848 | Doi | 10.1038/s42003-022-03715-z |
| Citation | Rios FJ, et al. (2022) TRPM7 deficiency exacerbates cardiovascular and renal damage induced by aldosterone-salt. Commun Biol 5(1):746 |
| abstractText | Hyperaldosteronism causes cardiovascular disease as well as hypomagnesemia. Mechanisms are ill-defined but dysregulation of TRPM7, a Mg(2+)-permeable channel/alpha-kinase, may be important. We examined the role of TRPM7 in aldosterone-dependent cardiovascular and renal injury by studying aldosterone-salt treated TRPM7-deficient (TRPM7(+/Deltakinase)) mice. Plasma/tissue [Mg(2+)] and TRPM7 phosphorylation were reduced in vehicle-treated TRPM7(+/Deltakinase) mice, effects recapitulated in aldosterone-salt-treated wild-type mice. Aldosterone-salt treatment exaggerated vascular dysfunction and amplified cardiovascular and renal fibrosis, with associated increased blood pressure in TRPM7(+/Deltakinase) mice. Tissue expression of Mg(2+)-regulated phosphatases (PPM1A, PTEN) was downregulated and phosphorylation of Smad3, ERK1/2, and Stat1 was upregulated in aldosterone-salt TRPM7-deficient mice. Aldosterone-induced phosphorylation of pro-fibrotic signaling was increased in TRPM7(+/Deltakinase) fibroblasts, effects ameliorated by Mg(2+) supplementation. TRPM7 deficiency amplifies aldosterone-salt-induced cardiovascular remodeling and damage. We identify TRPM7 downregulation and associated hypomagnesemia as putative molecular mechanisms underlying deleterious cardiovascular and renal effects of hyperaldosteronism. |
