| First Author | Moral-Sanz J | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 5034 |
| PubMed ID | 36028487 | Mgi Jnum | J:327974 |
| Mgi Id | MGI:7334272 | Doi | 10.1038/s41467-022-32568-7 |
| Citation | Moral-Sanz J, et al. (2022) AMPK deficiency in smooth muscles causes persistent pulmonary hypertension of the new-born and premature death. Nat Commun 13(1):5034 |
| abstractText | AMPK has been reported to facilitate hypoxic pulmonary vasoconstriction but, paradoxically, its deficiency precipitates pulmonary hypertension. Here we show that AMPK-alpha1/alpha2 deficiency in smooth muscles promotes persistent pulmonary hypertension of the new-born. Accordingly, dual AMPK-alpha1/alpha2 deletion in smooth muscles causes premature death of mice after birth, associated with increased muscularisation and remodeling throughout the pulmonary arterial tree, reduced alveolar numbers and alveolar membrane thickening, but with no oedema. Spectral Doppler ultrasound indicates pulmonary hypertension and attenuated hypoxic pulmonary vasoconstriction. Age-dependent right ventricular pressure elevation, dilation and reduced cardiac output was also evident. KV1.5 potassium currents of pulmonary arterial myocytes were markedly smaller under normoxia, which is known to facilitate pulmonary hypertension. Mitochondrial fragmentation and reactive oxygen species accumulation was also evident. Importantly, there was no evidence of systemic vasculopathy or hypertension in these mice. Moreover, hypoxic pulmonary vasoconstriction was attenuated by AMPK-alpha1 or AMPK-alpha2 deletion without triggering pulmonary hypertension. |
