Medizinische Universität Graz - Research portal
Navigation/Search
- Researchers
- Institutions
- Projects
- Publications
- Partners
- Sponsors
- Equipment
- Knowhow
- Fields of Research
"Faces" of the day:
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Wei, X; Jin, J; Wu, J; He, Y; Guo, J; Yang, Z; Chen, L; Hu, K; Li, L; Jia, M; Li, Q; Lv, X; Ge, F; Ma, S; Wu, H; Zhi, X; Wang, X; Jiang, L; Osto, E; Zhang, J; Meng, D.
Cardiac-specific BACH1 ablation attenuates pathological cardiac hypertrophy by inhibiting the Ang II type 1 receptor expression and the Ca2+/CaMKII pathway.
Cardiovasc Res. 2023; 119(9): 1842-1855.
Doi: 10.1093/cvr/cvad086
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
- Osto Elena
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- AIMS: BACH1 is up-regulated in hypertrophic hearts, but its function in cardiac hypertrophy remains largely unknown. This research investigates the function and mechanisms of BACH1 in the regulation of cardiac hypertrophy. METHODS AND RESULTS: Male cardiac-specific BACH1 knockout mice or cardiac-specific BACH1 transgenic (BACH1-Tg) mice and their respective wild-type littermates developed cardiac hypertrophy induced by angiotensin II (Ang II) or transverse aortic constriction (TAC). Cardiac-specific BACH1 knockout in mice protected the hearts against Ang II- and TAC-induced cardiac hypertrophy and fibrosis, and preserved cardiac function. Conversely, cardiac-specific BACH1 overexpression markedly exaggerated cardiac hypertrophy and fibrosis and reduced cardiac function in mice with Ang II- and TAC-induced hypertrophy. Mechanistically, BACH1 silencing attenuated Ang II- and norepinephrine-stimulated calcium/calmodulin-dependent protein kinase II (CaMKII) signalling, the expression of hypertrophic genes, and hypertrophic growth of cardiomyocytes. Ang II stimulation promoted the nuclear localization of BACH1, facilitated the recruitment of BACH1 to the Ang II type 1 receptor (AT1R) gene promoter, and then increased the expression of AT1R. Inhibition of BACH1 attenuated Ang II-stimulated AT1R expression, cytosolic Ca2+ levels, and CaMKII activation in cardiomyocytes, whereas overexpression of BACH1 led to the opposite effects. The increased expression of hypertrophic genes induced by BACH1 overexpression upon Ang II stimulation was suppressed by CaMKII inhibitor KN93. The AT1R antagonist, losartan, significantly attenuated BACH1-mediated CaMKII activation and cardiomyocyte hypertrophy under Ang II stimulation in vitro. Similarly, Ang II-induced myocardial pathological hypertrophy, cardiac fibrosis, and dysfunction in BACH1-Tg mice were blunted by treatment with losartan. CONCLUSION: This study elucidates a novel important role of BACH1 in pathological cardiac hypertrophy by regulating the AT1R expression and the Ca2+/CaMKII pathway, and highlights potential therapeutic target in pathological cardiac hypertrophy.
- Find related publications in this database (using NLM MeSH Indexing)
- Mice - administration & dosage
- Male - administration & dosage
- Animals - administration & dosage
- Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism
- Calcium - metabolism
- Losartan - administration & dosage
- Cardiomegaly - metabolism
- Myocytes, Cardiac - metabolism
- Mice, Transgenic - administration & dosage
- Angiotensin II - metabolism
- Mice, Knockout - administration & dosage
- Fibrosis - administration & dosage
- Mice, Inbred C57BL - administration & dosage
- Find related publications in this database (Keywords)
- Cardiac hypertrophy
- BACH1
- Angiotensin II type 1 receptor
- CaMKII
- Cardiac myocyte