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Adiponectin Stimulates Angiogenesis by Promoting Cross-talk between AMP-activated Protein Kinase and Akt Signaling in Endothelial Cells
Open accessAbstract
Adiponectin is an adipocyte-specific adipocytokine with anti-atherogenic and anti-diabetic properties. Here, we investigated whether adiponectin regulates angiogenic processes in vitro and in vivo. Adiponectin stimulated the differentiation of human umbilical vein endothelium cells (HUVECs) into capillary-like structures in vitro and functioned as a chemoattractant in migration assays. Adiponectin promoted the phosphorylation of AMP-activated protein kinase (AMPK), protein kinase Akt/protein kinase B, and endothelial nitric oxide synthesis (eNOS) in HUVECs. Transduction with either dominant-negative AMPK or dominant-negative Akt abolished adiponectin-induced eNOS phosphorylation as well as adiponectin-stimulated HUVEC migration and differentiation. Dominant-negative AMPK also inhibited adiponectin-induced Akt phosphorylation, suggesting that AMPK is upstream of Akt. Dominant-negative Akt or the phosphatidylinositol 3-kinase inhibitor LY294002 blocked adiponectin-stimulated Akt and eNOS phosphorylation, migration, and differentiation without altering AMPK phosphorylation. Finally, adiponectin stimulated blood vessel growth in vivo in mouse Matrigel plug implantation and rabbit corneal models of angiogenesis. These data indicate that adiponectin can function to stimulate the new blood vessel growth by promoting cross-talk between AMP-activated protein kinase and Akt signaling within endothelial cells.
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“Further evidence also shows that AMPK lies upstream of the phosphatidylinositol-3-kinase-protein kinase B pathway, which also leads to eNOS activation and NO production [162,164,165].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [164]
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Cites
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419
Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance
Hotamisligil, G. S., Shargill, N. S., & Spiegelman, B. M. (1993) · Science · doi:10.1126/science.7678183 · Cited by 7,518
Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., et al. (2001) · Nature Medicine · doi:10.1038/90984 · Cited by 4,915
Paradoxical Decrease of an Adipose-Specific Protein, Adiponectin, in Obesity
Arita, Y., Kihara, S., Ouchi, N., Takahashi, M., Maeda, K., Miyagawa, J.-I., Hotta, K., Shimomura, I., Nakamura, T., Miyaoka, K., et al. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0255 · Cited by 4,856
Angiogenesis in health and disease
Carmeliet, P. (2003) · Nature Medicine · doi:10.1038/nm0603-653 · Cited by 4,379
Yamauchi, T., Kamon, J., Minokoshi, Y., Ito, Y., Waki, H., Uchida, S., Yamashita, S., Noda, M., Kita, S., Ueki, K., et al. (2002) · Nature Medicine · doi:10.1038/nm788 · Cited by 4,238
Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation
Dimmeler, S., Fleming, I., Fisslthaler, B., Hermann, C., Busse, R., & Zeiher, A. M. (1999) · Nature · doi:10.1038/21224 · Cited by 3,591
Cloning of adiponectin receptors that mediate antidiabetic metabolic effects
Yamauchi, T., Kamon, J., Ito, Y., Tsuchida, A., Yokomizo, T., Kita, S., Sugiyama, T., Miyagishi, M., Hara, K., Tsunoda, M., et al. (2003) · Nature · doi:10.1038/nature01705 · Cited by 3,176
Plasma Concentrations of a Novel, Adipose-Specific Protein, Adiponectin, in Type 2 Diabetic Patients
Hotta, K., Funahashi, T., Arita, Y., Takahashi, M., Matsuda, M., Okamoto, Y., Iwahashi, H., Kuriyama, H., Ouchi, N., Maeda, K., et al. (2000) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.20.6.1595 · Cited by 3,133
Regulation of endothelium-derived nitric oxide production by the protein kinase Akt
Fulton, D. J., Gratton, J., McCabe, T. J. D., Fontana, J. T., Fujio, Y., Walsh, K. X., Franke, T. F., Papapetropoulos, A., & Sessa, W. C. (1999) · Nature · doi:10.1038/21218 · Cited by 2,616
Research works printed but not linked: 1
- Phillips, 1994, In Vivo (Athens)., 8, 961
Cited by
Sorted by citations
Items 101–200 of 757
AMP-Activated Protein Kinase: A Key Stress Signaling Pathway in the Heart
Young, L. H., Li, J., Baron, S. J., & Russell, R. R. (2005) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2005.04.005 · Cited by 165
Adiponectin directly improves endothelial dysfunction in obese rats through the AMPK–eNOS Pathway
Deng, G., Long, Y., Yu, Y.-R., & Li, M.-R. (2009) · International Journal of Obesity · doi:10.1038/ijo.2009.205 · Cited by 165
Kambara, T., Ohashi, K., Shibata, R., Ogura, Y., Maruyama, S., Enomoto, T., Uemura, Y., Shimizu, Y., Yuasa, D., Matsuo, K., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.357939 · Cited by 160
“In some experiments, cells were infected with an adenoviral vector encoding c-Myc-tagged dominantnegative AMPK (Ad-dnAMPK) or Ad- -gal as a control at a multiplicity of infection of 10 for 24 h (22), followed by treatment with CTRP9 or vehicle.”
MethodShibata, S., Tada, Y., Asano, Y., Hau, C. S., Kato, T., Saeki, H., Yamauchi, T., Kubota, N., Kadowaki, T., & Sato, S. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1101739 · Cited by 160
“It has been reported that the ERK signaling pathway is activated as a downstream signal molecule of adiponectin receptors in several cell types, including endothelial cells, macrophages, cardiac fibroblasts, and pancreatic cells (10, 41, 53, 54).”
BackgroundRole of the energy sensor AMP-activated protein kinase in renal physiology and disease
Hallows, K. R., Mount, P. F., Pastor‐Soler, N. M., & Power, D. A. (2010) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00005.2010 · Cited by 158
“Activation of AMPK in endothelial cells has been reported in response to multiple and diverse stimuli, including shear stress (20), ATP depletion (95, 144), hormones such as adiponectin (18, 20, 99), bradykinin (96) and thrombin (116), the drugs metformin (143) and atorvastatin (20), and the free radical peroxynitrite…”
Leptin, the obesity‐associated hormone, exhibits direct cardioprotective effects
Smith, C. C. T., Mocanu, M. M., Davidson, S. M., Wynne, A. M., Simpkin, J. C., & Yellon, D. M. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706834 · Cited by 153
“Thus, adiponectin, another adipocytokine, was shown to stimulate angiogenesis by promoting crosstalk between AMPK and Akt (Ouchi et al., 2004).”
BackgroundAdipolin/C1qdc2/CTRP12 Protein Functions as an Adipokine That Improves Glucose Metabolism
Enomoto, T., Ohashi, K., Shibata, R., Higuchi, A., Maruyama, S., Izumiya, Y., Walsh, K. X., Murohara, T., & Ouchi, N. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.277319 · Cited by 155
Visfatin promotes angiogenesis by activation of extracellular signal-regulated kinase 1/2
Kim, S.-R., Bae, S., Choi, K., Park, S.-Y., Jun, H. O., Lee, J. Y., Jang, H., Yun, I., Yoon, K., Kim, Y.-J., et al. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.03.105 · Cited by 152
Caballero, A. E., Delgado, A., Aguilar-Salinas, C. A., Herrera, A. N., Castillo, J. L., Cabrera, T., Gomez-Perez, F. J., & Rull, J. A. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0019 · Cited by 151
Cross-talk between adipose tissue and vasculature: role of adiponectin
Li, F. Y. L., Cheng, K. K. Y., Lam, K. S. L., Vanhoutte, P. M., & Xu, A. (2010) · Acta Physiologica · doi:10.1111/j.1748-1716.2010.02216.x · Cited by 155
Paradoxic effects of metformin on endothelial cells and angiogenesis
Dallaglio, K., Bruno, A., Cantelmo, A. R., Esposito, A. I., Ruggiero, L., Orecchioni, S., Calleri, A., Bertolini, F., Pfeffer, U., Noonan, D. M., et al. (2014) · Carcinogenesis · doi:10.1093/carcin/bgu001 · Cited by 146
Proangiogenic Contribution of Adiponectin toward Mammary Tumor Growth In vivo
Landskroner-Eiger, S., Qian, B., Muise, E. S., Nawrocki, A. R., Berger, J. P., Fine, E. J., Koba, W., Deng, Y., Pollard, J. W., & Scherer, P. E. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2649 · Cited by 145
“Previous work has proposed a role for APN in vessel remodeling and promotion of angiogenesis in an in vivo hind limb model of ischemia (25, 37).”
BackgroundThe ‘beneficial’ adipokines in reproduction and fertility
Campos, D. B., Palin, M., Bordignon, V., & Murphy, B. D. (2007) · International Journal of Obesity · doi:10.1038/sj.ijo.0803719 · Cited by 150
Carattino, M. D., Edinger, R. S., Grieser, H. J., Wise, R., Neumann, D., Schlattner, U., Johnson, J. P., Kleyman, T. R., & Hallows, K. R. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501770200 · Cited by 145
Adiponectin-Resistance in Obesity
Engin, A. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-48382-5_18 · Cited by 149
Chandrasekar, B., Boylston, W. H., Venkatachalam, K., Webster, N. J. G., Prabhu, S. D., & Valente, A. J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804236200 · Cited by 145
Epoxyeicosatrienoic Acid Agonist Rescues the Metabolic Syndrome Phenotype of HO-2-Null Mice
Sodhi, K., Inoue, K., Gotlinger, K. H., Canestraro, M., Vanella, L., Kim, D., Manthati, V. L., Koduru, S. R., Falck, J. R., Schwartzman, M. L., et al. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.157545 · Cited by 143
“Adiponectin is critical for endothelial cell survival and function through the activation of eNOS, via crosstalk between pAKT and pAMPK (Ouchi et al., 2004; Wang and Scherer, 2008).”
BackgroundAMPK exerts dual regulatory effects on the PI3K pathway
Tao, R., Gong, J., Luo, X., Zang, M., Guo, W., Wen, R., & Luo, Z. (2010) · Journal of Molecular Signaling · doi:10.1186/1750-2187-5-1 · Cited by 152
“AMPK has been reported to regulate IRS1 [4-6] and Akt/PKB [7-12], while insulin and Akt have negative impacts on AMPK activation [13-15].”
BackgroundResultInfluentialWang, Y., Gao, E., Tao, L., Lau, W. B., Yuan, Y., Goldstein, B. J., Lopez, B. L., Christopher, T. A., Tian, R., Koch, W. J., et al. (2009) · Circulation · doi:10.1161/circulationaha.108.815043 · Cited by 136
Cardiac myocyte follistatin-like 1 functions to attenuate hypertrophy following pressure overload
Shimano, M., Ouchi, N., Nakamura, K., van Wijk, B., Ohashi, K., Asaumi, Y., Higuchi, A., Pimentel, D. R., Sam, F., Murohara, T., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1108559108 · Cited by 136
“These effects on myocardial capillarization are consistent with the previously described angiogenic functions of Fstl1 (31) and AMPK signaling (32, 34, 37).”
BackgroundTosca, L., Froment, P., Solnais, P., Ferré, P., Foufelle, F., & Dupont, J. (2005) · Endocrinology · doi:10.1210/en.2005-0301 · Cited by 146
“ing endothelial cells (57) and the myocardium (58).”
BackgroundLee, M., Klein, R. L., El‐Shewy, H. M., Luttrell, D. K., & Luttrell, L. M. (2008) · Biochemistry · doi:10.1021/bi801451f · Cited by 137
“In endothelial cells, activation of the AMPK and Akt pathways by adiponectin stimulates angiogenesis and nitric oxide production (21,22).”
BackgroundAdiponectin as a potential biomarker of vascular disease
Mohammadi, S., Arefhosseini, S. R., Ebrahimi‐Mameghani, M., Fallah, P., & Bazi, Z. (2015) · Vascular Health and Risk Management · doi:10.2147/vhrm.s48753 · Cited by 129
DIP2A Functions as a FSTL1 Receptor
Ouchi, N., Asaumi, Y., Ohashi, K., Higuchi, A., Sono-Romanelli, S., Oshima, Y., & Walsh, K. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.069468 · Cited by 128
Ohashi, K., Ouchi, N., & Matsuzawa, Y. (2011) · American Journal of Hypertension · doi:10.1038/ajh.2010.216 · Cited by 127
Self-citationMolecular Mechanisms of Ghrelin-Mediated Endothelial Nitric Oxide Synthase Activation
Xu, X., Jhun, B. S., Ha, C. H., & Jin, Z. (2008) · Endocrinology · doi:10.1210/en.2008-0255 · Cited by 127
“phorylation and NO production in ECs are only dependent on AMPK, but not Akt (48).”
BackgroundDifferential Effects of Leptin and Adiponectin in Endothelial Angiogenesis
Adya, R., Tan, B. K., & Randeva, H. S. (2015) · Journal of Diabetes Research · doi:10.1155/2015/648239 · Cited by 130
“Finally, since AMP-activated protein kinase (AMPK), a stress-activated protein kinase, and Akt have been implicated as critical mediators of adiponectin induced angiogenesis in both normoxic and ischemic tissues, we examined the role of these signalling pathways in gAd induced endothelial angiogenesis [31].”
BackgroundResultInfluentialde la Torre, N. G., Rubio, M. Á., Bordiú, E., Cabrerizo, L., Aparicio, E., Hernández, C., Sánchez-Pernaute, A., Díez-Valladares, L. I., Torres, A. J., Puente, M., et al. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1370 · Cited by 126
“Some studies showed that adiponectin can stimulate new blood vessel formation in ischemic tissue ( 15 ), and stimulate the differentiation of humanendothelialcellsintocapillarylikestructuresinvitroand blood vessel growth in vivo in a rabbit corneal assay (16).”
BackgroundBurgess, A., Li, M., Vanella, L., Kim, D. H., Rezzani, R., Rodella, L. F., Sodhi, K., Canestraro, M., Pavel Martasek, E., Peterson, S. J., et al. (2010) · Hypertension · doi:10.1161/hypertensionaha.110.151423 · Cited by 126
PGC-1α mediates exercise-induced skeletal muscle VEGF expression in mice
Leick, L., Hellsten, Y., Fentz, J., Lyngby, S. S., Wojtaszewski, J. F. P., Hidalgo, J., & Pilegaard, H. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00076.2009 · Cited by 126
Wang, Y., Zhang, X., Shao, J., Liu, H., Liu, X., & Luo, E. (2017) · Scientific Reports · doi:10.1038/s41598-017-03899-z · Cited by 125
Kondo, M., Shibata, R., Miura, R., Shimano, M., Kondo, K., Li, P., Ohashi, T., Kihara, S., Maeda, N., Walsh, K., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805301200 · Cited by 124
Eringa, E. C., Serné, E. H., Meijer, R. I., Schalkwijk, C. G., Houben, A. J. H. M., Stehouwer, C. D. A., Smulders, Y. M., & van Hinsbergh, V. W. M. (2013) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-013-9239-7 · Cited by 126
“These include NO-dependent vasodilatation and muscle perfusion [90, 91], angiogenesis [92] and inflammation [93].”
BackgroundMeijer, R. I., Bakker, W., Alta, C.-L. F., Sipkema, P., Yudkin, J. S., Viollet, B., Richter, E. A., Smulders, Y. M., van Hinsbergh, V. W. M., Serné, E. H., et al. (2012) · Diabetes · doi:10.2337/db11-1603 · Cited by 123
“Previous studies have indeed shown that adiponectin can activate AMPK in endothelial cells (30), and previous data from our group have shown that adiponectin uncovers insulininduced vasodilation in muscle resistance arteries through AMPK (31).”
ResultAdiponectin: a link between obesity and cancer
Barb, D., Pazaitou‐Panayiotou, K., & Mantzoros, C. S. (2006) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.15.8.917 · Cited by 125
“fAd stimulates the differentiation of human umbilical vein endothelial cells into a capillary-like structure by promoting cross talk between AMP-activated protein kinase and Akt signalling [126].”
BackgroundIrisin improves endothelial function in obese mice through the AMPK-eNOS pathway
Han, F., Zhang, S., Hou, N., Wang, D., & Sun, X. (2015) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00443.2015 · Cited by 122
Kim, E. J., Jung, S., Son, K. H., Kim, S. R., Ha, T. Y., Park, M. G., Jo, I. G., Park, J. G., Choe, W., Kim, S. S., et al. (2007) · Molecular Pharmacology · doi:10.1124/mol.107.034447 · Cited by 122
“On the contrary, several lines of evidence also seem to suggest that AMPK functions upstream of Akt signaling (Ouchi et al., 2004), and another report has shown that AMPK is activated in a PI-3 kinase-dependent manner upon the exposure of endothelial cells to oxidants such as ONOO (Zou et al.”
BackgroundAdiponectin in Cardiovascular Inflammation and Obesity
Aprahamian, T. R., & Sam, F. (2011) · International Journal of Inflammation · doi:10.4061/2011/376909 · Cited by 124
“This has been demonstrated using mouse models of tissue ischemia and cardiac remodeling as well as rabbit corneal models of angiogenesis [20, 64, 65].”
MethodInflamed adipose tissue, insulin resistance and vascular injury
Andersson, C. X., Gustafson, B., Hammarstedt, A., Hedjazifar, S., & Smith, U. (2008) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.889 · Cited by 118
Miyazaki, T., Bub, J. D., Uzuki, M., & Iwamoto, Y. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.05.076 · Cited by 118
Molecular mechanisms of alcoholic fatty liver: role of sterol regulatory element-binding proteins
You, M., & Crabb, D. W. (2004) · Alcohol · doi:10.1016/j.alcohol.2004.07.004 · Cited by 119
Adiponectin, obesity, and cardiovascular disease
Faßhauer, M., Paschke, R., & Stümvoll, M. (2004) · Biochimie · doi:10.1016/j.biochi.2004.09.016 · Cited by 120
Youn, J. Y., Wang, T., & Cai, H. “. (2008) · Circulation Research · doi:10.1161/circresaha.108.178467 · Cited by 117
Wang, X., Satoh, H., Kase, H., Suzuki, K., & Hattori, Y. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.04.111 · Cited by 116
Adiponectin Is Required for PPARγ-Mediated Improvement of Endothelial Function in Diabetic Mice
Wong, W. T., Tian, X. Y., Xu, A., Yu, J. Q., Lau, C. W., Hoo, R. L. C., Wang, Y., Lee, V. W. Y., Lam, K. S. L., Vanhoutte, P. M., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.05.009 · Cited by 115
AMP‐ACTIVATED PROTEIN KINASE ACTIVATION AS A STRATEGY FOR PROTECTING VASCULAR ENDOTHELIAL FUNCTION
Zou, M., & Wu, Y. (2007) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2007.04851.x · Cited by 116
Kim, K.-Y., Kim, J. K., Jeon, J. H., Yoon, S. R., Choi, I., & Yang, Y. D. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.12.026 · Cited by 121
Epoxyeicosatrienoic acids are part of the VEGF-activated signaling cascade leading to angiogenesis
Webler, A. C., Michaelis, U. R., Popp, R., Barbosa‐Sicard, E., Murugan, A., Falck, J. R., Fißlthaler, B., & Fleming, I. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00230.2008 · Cited by 115
“In the search to identify the molecular mechanism(s) underlying the VEGF-induced increase in CYP2C expression, we analyzed the role of the AMPK as VEGF has previously been demonstrated to activate the kinase in endothelial cells (36), and activation of AMPK has been linked to endothelial cell migration and angiogenesi…”
BackgroundJoki, Y., Ohashi, K., Yuasa, D., Shibata, R., Ito, M., Matsuo, K., Kambara, T., Uemura, Y., Hayakawa, S., Hiramatsu‐Ito, M., et al. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.02.081 · Cited by 114
AMP-activated protein kinase promotes the differentiation of endothelial progenitor cells
Li, X., Han, Y., Pang, W., Li, C., Xie, X., Shyy, J. Y.-J., & Zhu, Y. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.172452 · Cited by 113
Adiponectin mediates cardioprotection in oxidative stress-induced cardiac myocyte remodeling
Essick, E. E., Ouchi, N., Wilson, R. M., Ohashi, K., Ghobrial, J. M., Shibata, R., Pimentel, D. R., & Sam, F. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00428.2011 · Cited by 111
“Recombinant APN was prepared as previously described (39).”
Dual Roles of the AMP-Activated Protein Kinase Pathway in Angiogenesis
Li, Y., Sun, R., Zou, J., Ying, Y., & Luo, Z. (2019) · Cells · doi:10.3390/cells8070752 · Cited by 113
“Similar findings were reported using adiponectin as a proangiogenic factor [50].”
ResultEwart, M., & Kennedy, S. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.11.002 · Cited by 112
Adipose tissue, inflammation and cardiovascular disease
Ikeoka, D., Mader, J. K., & Pieber, T. R. (2010) · Revista da Associação Médica Brasileira · doi:10.1590/s0104-42302010000100026 · Cited by 110
Uemura, Y., Shibata, R., Ohashi, K., Enomoto, T., Kambara, T., Yamamoto, T., Ogura, Y., Yuasa, D., Joki, Y., Matsuo, K., et al. (2012) · The FASEB Journal · doi:10.1096/fj.12-213744 · Cited by 109
“In some experiments, VSMCs were infected with adenoviral vector encoding dominant-negative mutant forms of AMPK (Ad-dnAMPK) or Ad- -gal as a control at a multiplicity of infection of 10 for 24 h (25, 26).”
MethodShimano, M., Ouchi, N., Shibata, R., Ohashi, K., Pimentel, D. R., Murohara, T., & Walsh, K. X. (2010) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2010.02.021 · Cited by 111
“We have previously reported that adiponectin promotes ischemia-induced revascularization in skeletal muscle which is partly dependent on its ability to activate AMPK signaling [26,27,37].”
BackgroundThe role of adiponectin in human vascular physiology
Vaiopoulos, G., Marinou, K., Christodoulides, C., & Koutsilieris, M. (2011) · International Journal of Cardiology · doi:10.1016/j.ijcard.2011.07.047 · Cited by 108
Adipokines in reproductive function: a link between obesity and polycystic ovary syndrome
Chen, X., Jia, X., Qiao, J., Guan, Y., & Kang, J. (2013) · Journal of Molecular Endocrinology · doi:10.1530/jme-12-0247 · Cited by 112
“Several other signaling pathways have also been suggested, including PI3K/Akt and MAPK pathways (Ouchi et al. 2004, Luo et al. 2005).”
BackgroundRole of endothelial progenitor cells during ischemia-induced vasculogenesis and collateral formation
Tongers, J., Roncalli, J. G., & Losordo, D. W. (2010) · Microvascular Research · doi:10.1016/j.mvr.2010.01.012 · Cited by 106
“Notably, the extent of collateral formation and the number of circulating EPCs correlate inversely with insulin resistance, adiponectin level, PAI-1 concentration (He et al., 2006; Ouchi et al., 2004; Xiang et al., 2004) and with many of the characteristics associated with metabolic syndrome (i.”
BackgroundAssociation between plasma adiponectin levels and unstable coronary syndromes
Wolk, R. A., Berger, P. B., Lennon, R. J., Brilakis, E. S., Davison, D. E., & Somers, V. K. (2006) · European Heart Journal · doi:10.1093/eurheartj/ehl361 · Cited by 106
“Ever smoked, no. (%) 187 (56) 92 (55) 0.71 Current smoker, no. (%) 21 (6) 19 (11) 0.05 Hypertension, no. (%) 142 (43) 85 (51) 0.10 Family CAD history, no. (%) 80 (24) 47 (28) 0.36 Prior MI, no. (%) 26 (8) 51 ( 30 ) ,0.001 Systolic BP (mmHg) 135+ 26 129+ 25 0.01 Diastolic BP (mmHg) 73+ 13 72+ 10 0.56 Mean BP (mmHg) 99+…”
InfluentialPeterson, S. J., Kim, D. H., Li, M., Positano, V., Vanella, L., Rodella, L. F., Piccolomini, F., Puri, N., Gastaldelli, A., Kusmic, C., et al. (2009) · Journal of Lipid Research · doi:10.1194/jlr.m800610-jlr200 · Cited by 106
“pAKTand AMPK act as fuel sensors in the regulation of energy balance, and the resultant crosstalk of AMPK-AKT has been shown to regulate nitric oxide bioavailability and vascular function (56, 61, 62).”
BackgroundHeme oxygenase: the key to renal function regulation
Abraham, N. G., Cao, J. J., Sacerdoti, D., Li, X., & Drummond, G. (2009) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.90449.2008 · Cited by 102
“Our results support the report that adiponectin is critical for EC survival and function (144) via the activation of eNOS and pAKT and pAMPK.”
ResultMolecular mechanisms of signal transduction via adiponectin and adiponectin receptors
Heiker, J. T., Kosel, D., & Beck‐Sickinger, A. G. (2010) · Biological Chemistry · doi:10.1515/bc.2010.104 · Cited by 105
“Interestingly, it is known for a wide variety of GPCRs to internalize via clathrin-dependent pathways mainly dependent on receptor phosphorylation and/or ubiquitination by downstream effector molecules and arrestin binding (Marchese et al., 2008).”
BackgroundInfluentialZou, F., Mao, X., Wang, N., Liu, J., & Ouyang, J. (2009) · Acta Pharmacologica Sinica · doi:10.1038/aps.2009.168 · Cited by 104
Hadjadj, S., Aubert, R., Fumeron, F., Péan, F., Tichet, J., Roussel, R., Marre, M., & groups, S. A. D. S. (2005) · Diabetologia · doi:10.1007/s00125-005-1747-x · Cited by 102
“Interestingly, adiponectin can stimulate angiogenesis both in vitro and in vivo [26, 27].”
BackgroundKambara, T., Shibata, R., Ohashi, K., Matsuo, K., Hiramatsu‐Ito, M., Enomoto, T., Yuasa, D., Ito, M., Hayakawa, S., Ogawa, H., et al. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.01518-14 · Cited by 101
Xing, S.-S., Yang, X.-Y., Zheng, T., Li, W.-J., Wu, D., Chi, J.-Y., Bian, F., Bai, X.-L., Wu, G.-J., Zhang, Y.-Z., et al. (2015) · Vascular Pharmacology · doi:10.1016/j.vph.2015.07.004 · Cited by 99
Obesity, Inflammation, and Vascular Disease
Calabrò, P., & Yeh, E. T. H. (2007) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/1-4020-5688-5_3 · Cited by 101
“[90] The clinical and experimental evidence presented above suggests that adiponectin may have therapeutic value for cardiovascular disease, diabetes mellitus, and metabolic syndrome.”
BackgroundHutchinson, D. S., Chernogubova, E., Dallner, O. S., Cannon, B., & Bengtsson, T. (2005) · Diabetologia · doi:10.1007/s00125-005-1936-7 · Cited by 101
“Endothelial cells have been used to elucidate AMPK signalling and effects by several agents [29–31], which makes it difficult to elucidate the Fig.”
BackgroundSeino, Y., Hirose, H., Saito, I., & Itoh, H. (2007) · Metabolism · doi:10.1016/j.metabol.2007.06.015 · Cited by 99
“Recent studies have demonstrated that the HMW multimer form of adiponectin is the active form of this protein [6,24,25].”
BackgroundPlasma Adiponectin Levels and Sonographic Phenotypes of Subclinical Carotid Artery Atherosclerosis
Iglseder, B., Mackēvičs, V., Stadlmayer, A., Tasch, G., Ladurner, G., & Paulweber, B. (2005) · Stroke · doi:10.1161/01.str.0000190834.00284.fd · Cited by 97
Stahmann, N., Woods, A., Spengler, K., Heslegrave, A., Bauer, R., Krause, S., Viollet, B., Carling, D., & Heller, R. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.108688 · Cited by 100
Adipose tissue angiogenesis in obesity
Lemoine, A. Y., Ledoux, S., & Larger, É. (2013) · Thrombosis and Haemostasis · doi:10.1160/th13-01-0073 · Cited by 98
“The situation is even more complex for adiponectin, a factor linked to obesity and metabolic syndrome, which has been found to mediate opposite outcomes, both proangiogenic, through activation of adenosine monophosphate kinase in endothelial cells (30) and anti-angiogenic effects (5, 40).”
BackgroundL’Abbate, A., Neglia, D., Vecoli, C., Novelli, M., Ottaviano, V., Baldi, S., Barsacchi, R., Paolicchi, A., Masiello, P., Drummond, G. S., et al. (2007) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00826.2007 · Cited by 95
The role of insulin and the adipocytokines in regulation of vascular endothelial function
Ritchie, S. A., Ewart, M., Perry, C. G., Connell, J., & Salt, I. P. (2004) · Clinical Science · doi:10.1042/cs20040190 · Cited by 98
Human Adipose Tissue Extract Induces Angiogenesis and Adipogenesis In Vitro
Sarkanen, J., Kaila, V., Mannerström, B., Räty, S., Kuokkanen, H., Miettinen, S., & Ylikomi, T. J. (2011) · Tissue Engineering Part A · doi:10.1089/ten.tea.2010.0712 · Cited by 96
Adiponectin, an Unlocking Adipocytokine
Sun, Y., Xun, K., Wang, C., Zhao, H., Bi, H., Chen, X., & Wang, Y. (2009) · Cardiovascular Therapeutics · doi:10.1111/j.1755-5922.2008.00069.x · Cited by 95
“By responding to adiponectin, AMPK mediated glucose utilization and fatty-acid oxidation in adipocyte and in skeletal muscle cells [155,156], NO production and nitric oxide synthase activation in vascular endothelial cells [144,157], new blood vessel growth (angiogenesis) [158], heart ischemia-reperfusion injury prote…”
BackgroundAMP-activated protein kinase mediates VEGF-stimulated endothelial NO production
Reihill, J. A., Ewart, M., Hardie, D. G., & Salt, I. P. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.01.110 · Cited by 91
“A recent report indicates that CaMKK mediates thrombin- stimulated AMPK activation in HUVECs, but that AMPK does not underlie thrombin-stimulated eNOS Ser1177 phosphorylation [21].”
InfluentialPlasma adiponectin concentrations in non-pregnant, normal and overweight pregnant women
Nien, J. K., Mazaki‐Tovi, S., Romero, R. J., Erez, O., Kusanovic, J. P., Gotsch, F., Pineles, B. L., Gómez, R., Edwin, S. S., Mazor, M., et al. (2007) · Journal of Perinatal Medicine · doi:10.1515/jpm.2007.123 · Cited by 93
The role of adipokines in cardiovascular disease
Shibata, R., Ouchi, N., Ohashi, K., & Murohara, T. (2017) · Journal of Cardiology · doi:10.1016/j.jjcc.2017.02.006 · Cited by 97
Shibata, R., Sato, K., Kumada, M., Izumiya, Y., Sonoda, M., Kihara, S., Ouchi, N., & Walsh, K. X. (2007) · Cardiovascular Research · doi:10.1016/j.cardiores.2007.02.010 · Cited by 93
“Bacterially-produced mouse adiponectin was prepared as described previously [36].”
MethodMultifaceted roles of Adiponectin in cancer
Hebbard, L., & Ranscht, B. (2013) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2013.11.005 · Cited by 94
Adipocytokines, cardiovascular pathophysiology and myocardial protection
Smith, C., & Yellon, D. M. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.09.003 · Cited by 96
Tamura, T., Furukawa, Y., Taniguchi, R., Sato, Y., Ono, K., Horiuchi, H., Nakagawa, Y., Kita, T., & Kimura, T. (2007) · Circulation Journal · doi:10.1253/circj.71.623 · Cited by 91
Yan, H., & Ajuwon, K. M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0145940 · Cited by 91
“Adiponectin activates AMPK in multiple tissues [20–22], and insulin sensitivity is positively correlated to AMPK activity [18, 21].”
BackgroundMetabolic activation of AMP kinase in vascular smooth muscle
Rubin, L. J., Magliola, L., Feng, X., JONES, A. W., & Hale, C. C. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00075.2004 · Cited by 90
“Cross talk between AMPK and Akt has been demonstrated for several cell systems, including endothelial cells (27) and the myocardium (17).”
BackgroundHirose, H., Yamamoto, Y., Seino-Yoshihara, Y., Kawabe, H., & Saito, I. (2010) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.6106 · Cited by 89
Adiponectin promotes endothelial progenitor cell number and function
Shibata, R., Skurk, C., Ouchi, N., Galasso, G., Kondo, K., Ohashi, T., Shimano, M., Kihara, S., Murohara, T., & Walsh, K. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.04.006 · Cited by 87
“Consistent with the findings reported here, it has been shown that adiponectin stimulates nitric oxide production in endothelial cells through AMPK-dependent and AMPK-independent phosphorylation of endothelial nitric oxide synthase eNOS [10,20].”
BackgroundMethodInfluentialPu, J., Peng, G., Li, L., Na, H., Liu, Y., & Liu, P. (2011) · Journal of Lipid Research · doi:10.1194/jlr.m011254 · Cited by 86
Description of a local cardiac adiponectin system and its deregulation in dilated cardiomyopathy
Skurk, C., Wittchen, F., Suckau, L., Witt, H., Noutsias, M., Fechner, H., Schultheiss, H.-P., & Poller, W. C. (2008) · European Heart Journal · doi:10.1093/eurheartj/ehn136 · Cited by 86
Howard, J. M., Beddy, P., Ennis, D. P., Keogan, M. T., Pidgeon, G. P., & Reynolds, J. V. (2010) · British journal of surgery · doi:10.1002/bjs.7072 · Cited by 85
Tabandeh, M. R., Hosseini, A., Saeb, M., Kafi, M., & Saeb, S. (2010) · Theriogenology · doi:10.1016/j.theriogenology.2009.11.006 · Cited by 85
Adiponectin inhibits induction of TNF‐α/RANKL‐stimulated NFATc1 via the AMPK signaling
Yamaguchi, N., Kukita, T., Li, Y.-J., Kamio, N., Fukumoto, S., Nonaka, K., Ninomiya, Y., Hanazawa, S., & Yamashita, Y. (2008) · FEBS Letters · doi:10.1016/j.febslet.2007.12.037 · Cited by 86
Adiponectin deficiency: Role in chronic inflammation induced colon cancer
Saxena, A., Chumanevich, A. A., Fletcher, E., Larsen, B., Lattwein, K. R., Kaur, K., & Fayad, R. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.12.006 · Cited by 84
“AMPK has anti-inflammatory effects and has been considered as a potential therapeutic target for cancer [23–26].”
BackgroundA Novel Role for Adiponectin in the Regulation of Inflammation
Ouchi, N., & Walsh, K. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.165068 · Cited by 85
Nakamura, T., Funayama, H., Kubo, N., Yasu, T., Kawakami, M., Saito, M., Momomura, S.-I., & Ishikawa, S.-E. (2006) · Circulation Journal · doi:10.1253/circj.70.1557 · Cited by 84
Calabrò, P., & Yeh, E. T. H. (2008) · Current Hypertension Reports · doi:10.1007/s11906-008-0008-z · Cited by 84
“Adiponectin has novel vascular actions to directly stimulate production of nitric oxide in endothelial cells using PI3K-dependent pathways, which involve the phosphorylation of endothelial nitric oxide synthase by adenosine monophosphate–activated protein kinase (AMPK) [ 42 ].”
BackgroundMuscle-derived follistatin-like 1 functions to reduce neointimal formation after vascular injury
Miyabe, M., Ohashi, K., Shibata, R., Uemura, Y., Ogura, Y., Yuasa, D., Kambara, T., Kataoka, Y., Yamamoto, T., Matsuo, K., et al. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvu105 · Cited by 87
Ohashi, K., Ouchi, N., Sato, K., Higuchi, A., Ishikawa, T., Herschman, H. R., Kihara, S., & Walsh, K. X. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00126-09 · Cited by 83
“gel (BD Biosciences) was performed as previously described (39).”
BackgroundMethodInfluentialLeclerc, G. M., Leclerc, G. J., Fu, G., & Barredo, J. C. (2010) · Journal of Molecular Signaling · doi:10.1186/1750-2187-5-15 · Cited by 87
“Additive activation of AMPK and Akt has been shown to regulate important biological functions such as angiogenesis and glucose metabolism [48,49], suggesting that positive interactions exist between AMPK and Akt as we report here.”
Background
Metadata
- Authors
- Ouchi, N., Kobayashi, H., Kihara, S., Kumada, M., Sato, K., Inoue, T., Funahashi, T., & Walsh, K.
- Affiliations
- Boston University (US)
- The University of Osaka (JP)
- Corresponding author
- Walsh, Kenneth
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-01
- Volume
- 279
- Issue
- 2
- Pages
- 1304-1309
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC4374490
- OpenAlex
- W2008967025
- Cited by
- 759
- References
- 49
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 20 · 2023: 15 · 2022: 21 · 2021: 23 · 2020: 23 · 2019: 25 · 2018: 22 · 2017: 40 · 2016: 26 · 2015: 39 · 2014: 30 · 2013: 58 · 2012: 58
- FWCI
- 14.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Uehara Memorial Foundation
- National Institutes of Health (HD23681, AG15052)
- National Institute on Aging (R01AG015052, AG17241, R37AG015052, AG15052, R01AG017241)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-40197, R01AR040197)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD023681, HD23681)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- adiponectin, angiogenesis, AMPK, Akt signaling, endothelial cells, endothelial nitric oxide synthase, endothelial cell migration, endothelial differentiation, capillary tube formation, phosphatidylinositol 3-kinase, signaling crosstalk, blood vessel development
- MeSH terms
- Adenoviridae, Animals, Cell Differentiation, Cell Movement, Cells, Cultured, Chromones, Collagen, Drug Combinations, Endothelium, Vascular, Enzyme Inhibitors, Genes, Dominant, Humans, Laminin, Models, Biological, Morpholines, Multienzyme Complexes, Neovascularization, Pathologic, Phosphorylation, Proteins, Proteoglycans, Rabbits, Recombinant Proteins, Time Factors, Umbilical Veins, Blotting, Western, Signal Transduction, Protein Serine-Threonine Kinases, Nitric Oxide Synthase, Phosphatidylinositol 3-Kinases, Intercellular Signaling Peptides and Proteins, Endothelial Cells, Mice, Adiponectin, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III, AMP-Activated Protein Kinases
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