AMPK and the Challenge of Treating Hypoxic Pulmonary Hypertension
Hypoxic pulmonary hypertension (HPH) is characterized by sustained elevation of pulmonary artery pressure produced by vasoconstriction and hyperproliferative remodeling of the pulmonary artery and subsequent right ventricular hypertrophy (RVH). The search for therapeutic targets for cardiovascular p...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/11/6205 |
| _version_ | 1797493057727234048 |
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| author | Karen Flores Patricia Siques Julio Brito Silvia M. Arribas |
| author_facet | Karen Flores Patricia Siques Julio Brito Silvia M. Arribas |
| author_sort | Karen Flores |
| collection | DOAJ |
| description | Hypoxic pulmonary hypertension (HPH) is characterized by sustained elevation of pulmonary artery pressure produced by vasoconstriction and hyperproliferative remodeling of the pulmonary artery and subsequent right ventricular hypertrophy (RVH). The search for therapeutic targets for cardiovascular pathophysiology has extended in many directions. However, studies focused on mitigating high-altitude pulmonary hypertension (HAPH) have been rare. Because AMP-activated protein kinase (AMPK) is involved in cardiovascular and metabolic pathology, AMPK is often studied as a potential therapeutic target. AMPK is best characterized as a sensor of cellular energy that can also restore cellular metabolic homeostasis. However, AMPK has been implicated in other pathways with vasculoprotective effects. Notably, cellular metabolic stress increases the intracellular ADP/ATP or AMP/ATP ratio, and AMPK activation restores ATP levels by activating energy-producing catabolic pathways and inhibiting energy-consuming anabolic pathways, such as cell growth and proliferation pathways, promoting cardiovascular protection. Thus, AMPK activation plays an important role in antiproliferative, antihypertrophic and antioxidant pathways in the pulmonary artery in HPH. However, AMPK plays contradictory roles in promoting HPH development. This review describes the main findings related to AMPK participation in HPH and its potential as a therapeutic target. It also extrapolates known AMPK functions to discuss the less-studied HAPH context. |
| first_indexed | 2024-03-10T01:14:32Z |
| format | Article |
| id | doaj.art-c7ae32b8393e49d9b5fbfc6e2643473d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:14:32Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c7ae32b8393e49d9b5fbfc6e2643473d2023-11-23T14:11:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012311620510.3390/ijms23116205AMPK and the Challenge of Treating Hypoxic Pulmonary HypertensionKaren Flores0Patricia Siques1Julio Brito2Silvia M. Arribas3Institute of Health Studies, University Arturo Prat, Av. Arturo Prat 2120, Iquique 1110939, ChileInstitute of Health Studies, University Arturo Prat, Av. Arturo Prat 2120, Iquique 1110939, ChileInstitute of Health Studies, University Arturo Prat, Av. Arturo Prat 2120, Iquique 1110939, ChileDepartment of Physiology, University Autonoma of Madrid, 28049 Madrid, SpainHypoxic pulmonary hypertension (HPH) is characterized by sustained elevation of pulmonary artery pressure produced by vasoconstriction and hyperproliferative remodeling of the pulmonary artery and subsequent right ventricular hypertrophy (RVH). The search for therapeutic targets for cardiovascular pathophysiology has extended in many directions. However, studies focused on mitigating high-altitude pulmonary hypertension (HAPH) have been rare. Because AMP-activated protein kinase (AMPK) is involved in cardiovascular and metabolic pathology, AMPK is often studied as a potential therapeutic target. AMPK is best characterized as a sensor of cellular energy that can also restore cellular metabolic homeostasis. However, AMPK has been implicated in other pathways with vasculoprotective effects. Notably, cellular metabolic stress increases the intracellular ADP/ATP or AMP/ATP ratio, and AMPK activation restores ATP levels by activating energy-producing catabolic pathways and inhibiting energy-consuming anabolic pathways, such as cell growth and proliferation pathways, promoting cardiovascular protection. Thus, AMPK activation plays an important role in antiproliferative, antihypertrophic and antioxidant pathways in the pulmonary artery in HPH. However, AMPK plays contradictory roles in promoting HPH development. This review describes the main findings related to AMPK participation in HPH and its potential as a therapeutic target. It also extrapolates known AMPK functions to discuss the less-studied HAPH context.https://www.mdpi.com/1422-0067/23/11/6205AMPKhypoxic pulmonary hypertensionhigh altitudecardioprotection |
| spellingShingle | Karen Flores Patricia Siques Julio Brito Silvia M. Arribas AMPK and the Challenge of Treating Hypoxic Pulmonary Hypertension International Journal of Molecular Sciences AMPK hypoxic pulmonary hypertension high altitude cardioprotection |
| title | AMPK and the Challenge of Treating Hypoxic Pulmonary Hypertension |
| title_full | AMPK and the Challenge of Treating Hypoxic Pulmonary Hypertension |
| title_fullStr | AMPK and the Challenge of Treating Hypoxic Pulmonary Hypertension |
| title_full_unstemmed | AMPK and the Challenge of Treating Hypoxic Pulmonary Hypertension |
| title_short | AMPK and the Challenge of Treating Hypoxic Pulmonary Hypertension |
| title_sort | ampk and the challenge of treating hypoxic pulmonary hypertension |
| topic | AMPK hypoxic pulmonary hypertension high altitude cardioprotection |
| url | https://www.mdpi.com/1422-0067/23/11/6205 |
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