Article Dans Une Revue Cell Metabolism Année : 2024

Dietary intake and glutamine-serine metabolism control pathologic vascular stiffness

Kouamé Kan Firmin Akoumia
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Naveen V G Kumar
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Stephen Y Chan
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Résumé

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 remain 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 (PAAF). 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

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hal-05267388 , version 1 (18-09-2025)

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Nesrine S Rachedi, Ying Tang, Yi-Yin Tai, Jingsi Zhao, Caroline Chauvet, et al.. Dietary intake and glutamine-serine metabolism control pathologic vascular stiffness. Cell Metabolism, 2024, 36 (6), pp.1335-1350.e8. ⟨10.1016/j.cmet.2024.04.010⟩. ⟨hal-05267388⟩
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