Dietary intake and glutamine-serine metabolism control pathologic vascular stiffness Journal Article
| Authors: | Rachedi, N. S.; Tang, Y.; Tai, Y. Y.; Zhao, J.; Chauvet, C.; Grynblat, J.; Akoumia, K. K. F.; Estephan, L.; Torrino, S.; Sbai, C.; Ait-Mouffok, A.; Latoche, J. D.; Al Aaraj, Y.; Brau, F.; Abélanet, S.; Clavel, S.; Zhang, Y.; Guillermier, C.; Kumar, N. V. G.; Tavakoli, S.; Mercier, O.; Risbano, M. G.; Yao, Z. K.; Yang, G.; Ouerfelli, O.; Lewis, J. S.; Montani, D.; Humbert, M.; Steinhauser, M. L.; Anderson, C. J.; Oldham, W. M.; Perros, F.; Bertero, T.; Chan, S. Y. |
| Article Title: | Dietary intake and glutamine-serine metabolism control pathologic vascular stiffness |
| Abstract: | Perivascular collagen deposition by activated fibroblasts promotes vascular stiffening and drives cardiovascular diseases such as pulmonary hypertension (PH). Whether and how vascular fibroblasts rewire their metabolism to sustain collagen biosynthesis remains unknown. Here, we found that inflammation, hypoxia, and mechanical stress converge on activating the transcriptional coactivators YAP and TAZ (WWTR1) in pulmonary arterial adventitial fibroblasts (PAAFs). Consequently, YAP and TAZ drive glutamine and serine catabolism to sustain proline and glycine anabolism and promote collagen biosynthesis. Pharmacologic or dietary intervention on proline and glycine anabolic demand decreases vascular stiffening and improves cardiovascular function in PH rodent models. By identifying the limiting metabolic pathways for vascular collagen biosynthesis, our findings provide guidance for incorporating metabolic and dietary interventions for treating cardiopulmonary vascular disease. © 2024 Elsevier Inc. |
| Keywords: | metabolism; fibrosis; cardiovascular disease; nutrition; pulmonary hypertension; collagen metabolism; glutamine metabolism; serine metabolism; vascular fibroblast |
| Journal Title: | Cell Metabolism |
| Volume: | 36 |
| Issue: | 6 |
| ISSN: | 1550-4131 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2024-06-04 |
| Start Page: | 1335 |
| End Page: | 1350.e8 |
| Language: | English |
| DOI: | 10.1016/j.cmet.2024.04.010 |
| PUBMED: | 38701775 |
| PROVIDER: | scopus |
| PMCID: | PMC11152997 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- Source: Scopus |
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