ArticleActa pharmacologica Sinica2021
Caffeine promotes angiogenesis through modulating endothelial mitochondrial dynamics.
Article in Acta pharmacologica Sinica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Article
- Mitochondrial quality control mechanisms as molecular targets for impaired lung development: from fetuses to neonates.Respiratory research · 2025Review
- Caffeine toxicity in zebrafish - Neurobehavioral changes, developmental defects, and oxidative stress: A review.Biomolecules & biomedicine · 2025Review
- The Multifaceted Role of Mitochondria in Angiogenesis.International journal of molecular sciences · 2025Review
- Osteocalcin Ameliorates CUMS-Induced Depressive-Like Behaviors by Reducing Mitochondrial Damage in Hippocampal Neurons.CNS neuroscience & therapeutics · 2025Article
- Caffeine as an Active Molecule in Cosmetic Products for Hair Loss: Its Mechanisms of Action in the Context of Hair Physiology and Pathology.Molecules (Basel, Switzerland) · 2025Review
- Decreasing mitochondrial fission ameliorates HIF-1α-dependent pathological retinal angiogenesis.Acta pharmacologica Sinica · 2024Article
- Caffeine and neonatal acute kidney injury.Pediatric nephrology (Berlin, Germany) · 2024Review
- Biodegradable Zn-5Dy Alloy with Enhanced Osteo/Angio-Genic Activity and Osteointegration Effect via Regulation of SIRT4-Dependent Mitochondrial Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Mitochondrial Dysfunction in Endothelial Progenitor Cells: Unraveling Insights from Vascular Endothelial Cells.Biology · 2024Review
- Caffeine improves mitochondrial dysfunction in the white matter of neonatal rats with hypoxia-ischemia through deacetylation: a proteomic analysis of lysine acetylation.Frontiers in molecular neuroscience · 2024Article
- Vitamin B12 Supplementation Improves Oocyte Development by Modulating Mitochondria and Yolk Protein in a Caffeine-IngestedAntioxidants (Basel, Switzerland) · 2023Article
- Microcirculation and Mitochondria: The Critical Unit.Journal of clinical medicine · 2023Review
- Mitochondria in endothelial cells angiogenesis and function: current understanding and future perspectives.Journal of translational medicine · 2023Review
- SZC-6, a small-molecule activator of SIRT3, attenuates cardiac hypertrophy in mice.Acta pharmacologica Sinica · 2023Article
- Mitochondrial dynamics in vascular remodeling and target-organ damage.Frontiers in cardiovascular medicine · 2023Review
- Caffeine reduces oxidative stress to protect against hyperoxia-induced lung injury via the adenosine A2A receptor/cAMP/PKA/Src/ERK1/2/p38MAPK pathway.Redox report : communications in free radical research · 2022Article
- Emerging Role of cAMP/AMPK Signaling.Cells · 2022Review
- Mitochondrial dysfunction in vascular endothelial cells and its role in atherosclerosis.Frontiers in physiology · 2022Review
- Caffeine Inhibits Direct and Indirect Angiogenesis in Zebrafish Embryos.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Caffeine induces multiple vascular effects. In this study we investigated the angiogenic effect of physiological concentrations of caffeine with focus on endothelial cell behaviors (migration and proliferation) during angiogenesis and its mitochondrial and bioenergetic mechanisms. We showed that caffeine (10-50 μM) significantly enhanced angiogenesis in vitro, evidenced by concentration-dependent increases in tube formation, and migration of human umbilical vein endothelial cells (HUVECs) without affecting cell proliferation. Caffeine (50 μM) enhanced endothelial migration via activation of cAMP/PKA/AMPK signaling pathway, which was mimicked by cAMP analog 8-Br-cAMP, and blocked by PKA inhibitor H89, adenylate cyclase inhibitor SQ22536 or AMPK inhibitor compound C. Furthermore, caffeine (50 μM) induced significant mitochondrial shortening through the increased phosphorylation of mitochondrial fission protein dynamin-related protein 1 (Drp1) in HUVECs, which increased its activity to regulate mitochondrial fission. Pharmacological blockade of Drp1 by Mdivi-1 (10 μM) or disturbance of mitochondrial fission by Drp1 silencing markedly suppressed caffeine-induced lamellipodia formation and endothelial cell migration. Moreover, we showed that caffeine-induced mitochondrial fission led to accumulation of more mitochondria in lamellipodia regions and augmentation of mitochondrial energetics, both of which were necessary for cell migration. In a mouse model of hindlimb ischemia, administration of caffeine (0.05% in 200 mL drinking water daily, for 14 days) significantly promoted angiogenesis and perfusion as well as activation of endothelial AMPK signaling in the ischemic hindlimb. Taken together, caffeine induces mitochondrial fission through cAMP/PKA/AMPK signaling pathway. Mitochondrial fission is an integral process in caffeine-induced endothelial cell migration by altering mitochondrial distribution and energetics.
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