Caffeine promotes angiogenesis through modulating endothelial mitochondrial dynamics

Wang, Litao; He, Pengcheng; Li, Anqi; Cao, Kaixiang; Yan, Jingwei; Guo, Shuai; Jiang, Lei; Yao, Lin; Dai, Xiaoyan; Feng, Du; Xu, Yiming; Tan, Ning

doi:10.1038/s41401-021-00623-6

Cited by 23 publications

(17 citation statements)

References 51 publications

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“…In a hindlimb ischemia model, treatment with caffeine-activated cAMP/PKA/AMPK signaling, led to enhanced mitochondrial biogenesis (Drp1 activation) and angiogenesis [ 87 ]. However, the mechanism of PKA-mediated AMPK activation was not examined in this study.…”

Section: Functional and Translational Significance Of The Camp/ampk Axismentioning

confidence: 99%

Emerging Role of cAMP/AMPK Signaling

Aslam

Ladilov

2022

Cells

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The 5′-Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a natural energy sensor in mammalian cells that plays a key role in cellular and systemic energy homeostasis. At the cellular level, AMPK supports numerous processes required for energy and redox homeostasis, including mitochondrial biogenesis, autophagy, and glucose and lipid metabolism. Thus, understanding the pathways regulating AMPK activity is crucial for developing strategies to treat metabolic disorders. Mounting evidence suggests the presence of a link between cyclic AMP (cAMP) and AMPK signaling. cAMP signaling is known to be activated in circumstances of physiological and metabolic stress due to the release of stress hormones, such as adrenaline and glucagon, which is followed by activation of membrane-bound adenylyl cyclase and elevation of cellular cAMP. Because the majority of physiological stresses are associated with elevated energy consumption, it is not surprising that activation of cAMP signaling may promote AMPK activity. Aside from the physiological role of the cAMP/AMPK axis, numerous reports have suggested its role in several pathologies, including inflammation, ischemia, diabetes, obesity, and aging. Furthermore, novel reports have provided more mechanistic insight into the regulation of the cAMP/AMPK axis. In particular, the role of distinct cAMP microdomains generated by soluble adenylyl cyclase in regulating basal and induced AMPK activity has recently been demonstrated. In the present review, we discuss current advances in the understanding of the regulation of the cAMP/AMPK axis and its role in cellular homeostasis and explore some translational aspects.

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Section: Functional and Translational Significance Of The Camp/ampk Axismentioning

confidence: 99%

Emerging Role of cAMP/AMPK Signaling

Aslam

Ladilov

2022

Cells

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“…In addition, in keeping with a direct effect on endothelial cells, caffeine induces apoptosis in human umbilical vein endothelial cells (HUVECs) [ 17 ]. In contrast with these observations, caffeine has been proposed to stimulate HUVEC migration and morphogenesis by altering mithocondrial distribution and energetics [ 22 ]. Finally, caffeine has been shown to decrease LPS-induced nitric oxide production in zebrafish embryos, suggesting the possibility that caffeine may also exert anti-angiogenic effects via an indirect mechanism of action following the suppression of pro-inflammatory responses [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Caffeine Inhibits Direct and Indirect Angiogenesis in Zebrafish Embryos

Basnet

Zizioli

Muscò

et al. 2021

IJMS

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In this study, we report the effects of caffeine on angiogenesis in zebrafish embryos both during normal development and after exposure to Fibroblast Growth Factor 2 (FGF2). As markers of angiogenesis, we measured the length and width of intersegmental vessels (ISVs), performed whole-mount in situ hybridization with fli1 and cadh5 vascular markers, and counted the number of interconnecting vessels (ICVs) in sub-intestinal venous plexus (SIVP). In addition, we measured angiogenesis after performing zebrafish yolk membrane (ZFYM) assay with microinjection of fibroblast growth factor 2 (FGF2) and perivitelline tumor xenograft assay with microinjection of tumorigenic FGF2-overexpressing endothelial (FGF2-T-MAE) cells. The results showed that caffeine treatment causes a shortening and thinning of ISVs along with a decreased expression of the vascular marker genes and a decrease in the number of ICVs in the SIVP. Caffeine was also able to block angiogenesis induced by exogenous FGF2 or FGF2-producing cells. Overall, our results are suggestive of the inhibitory effect of caffeine in both direct and indirect angiogenesis.

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“…15 Thus, therapeutic targeting of mitochondrial dynamics appears to be a promising therapeutic strategy for treating or preventing cardiovascular disease onset. 16,17 Recently, nanomedicine-based therapeutic approaches have been proved to be promising strategies for monitoring, diagnosis, and treatment of various disorders, including chronic cardiovascular and inflammatory diseases. 18,19 A recent special focus has been made on probing the ability of nanoparticles (NPs) to ameliorate various diseases, including aging, neurodegenerative, and cardiovascular diseases, and the inhibitory effects of NPs appear to be mediated through their antioxidant properties.…”

Section: ■ Introductionmentioning

confidence: 99%

“…The excessive total cellular and mitochondrial ROS, in turn, impair the mitochondrial respiratory chain, exacerbate oxidative stress, and further induce mitochondrial dysfunction, resulting in a variety of cellular dysfunctions, which are linked to the progression of various cardiovascular diseases . Thus, therapeutic targeting of mitochondrial dynamics appears to be a promising therapeutic strategy for treating or preventing cardiovascular disease onset. , …”

Section: Introductionmentioning

confidence: 99%

Flower-Like Molybdenum Disulfide Nanostructures for Promoting Mitochondrial Homeostasis and Attenuating Inflammatory Endothelial Dysfunction

Yang

Wang

et al. 2021

ACS Appl. Nano Mater.

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Mitochondrial dynamics is crucial to cellular metabolic homeostasis, development, and remodeling. However, the perturbation of mitochondrial dynamics impairs endothelial functions, leading to numerous diseases, including cardiovascular diseases. The few-layered molybdenum disulfide (MoS 2 )-based nanoagents hold great potential as therapeutic agents for various disorders. Herein, we investigated whether flower-like MoS 2 nanosheets (FL-MoS 2 ) promote mitochondrial homeostasis via modulating mitochondrial dynamics in endothelial cells. Our results demonstrated that mitochondrial elements become dramatically elongated in endothelial cells in response to FL-MoS 2 , suggesting that FL-MoS 2 promotes mitochondrial fusion rather than fission. The molecular mechanisms mediating mitochondrial fusion by FL-MoS 2 involved the upregulation of pro-fusion proteins as well as a decrease in mitochondrial translocation of dynamin-related protein 1 (Drp1). Consistently, we demonstrated that FL-MoS 2 maintains mitochondrial homeostasis through regulating transcription factor EB (TFEB)-mediated mitochondrial dynamics and biogenesis. In addition, we established that mitochondrial tubulation in response to FL-MoS 2 protects endothelial cells from mitochondrial impairments induced by tumor necrosis factor (TNF) α. Our results revealed the unique ability of MoS 2 -based nanoagents to modulate mitochondrial homeostasis, contributing to improvements in endothelial functions.

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Caffeine promotes angiogenesis through modulating endothelial mitochondrial dynamics

Cited by 23 publications

References 51 publications

Emerging Role of cAMP/AMPK Signaling

Emerging Role of cAMP/AMPK Signaling

Caffeine Inhibits Direct and Indirect Angiogenesis in Zebrafish Embryos

Flower-Like Molybdenum Disulfide Nanostructures for Promoting Mitochondrial Homeostasis and Attenuating Inflammatory Endothelial Dysfunction

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