Physical Exercise Protects Against Endothelial Dysfunction in Cardiovascular and Metabolic Diseases.
Endothelium dysfunction
Exercise
Therapeutic targets
Vascular disease
Journal
Journal of cardiovascular translational research
ISSN: 1937-5395
Titre abrégé: J Cardiovasc Transl Res
Pays: United States
ID NLM: 101468585
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
15
07
2021
accepted:
02
09
2021
pubmed:
18
9
2021
medline:
24
6
2022
entrez:
17
9
2021
Statut:
ppublish
Résumé
Increasing evidence shows that endothelial cells play critical roles in maintaining vascular homeostasis, regulating vascular tone, inhibiting inflammatory response, suppressing lipid leakage, and preventing thrombosis. The damage or injury of endothelial cells induced by physical, chemical, and biological risk factors is a leading contributor to the development of mortal cardiovascular and cerebrovascular diseases. However, the underlying mechanism of endothelial injury remains to be elucidated. Notably, no drugs effectively targeting and mending injured vascular endothelial cells have been approved for clinical practice. There is an urgent need to understand pathways important for repairing injured vasculature that can be targeted with novel therapies. Exercise training-induced protection to endothelial injury has been well documented in clinical trials, and the underlying mechanism has been explored in animal models. This review mainly summarizes the protective effects of exercise on vascular endothelium and the recently identified potential therapeutic targets for endothelial dysfunction.
Identifiants
pubmed: 34533746
doi: 10.1007/s12265-021-10171-3
pii: 10.1007/s12265-021-10171-3
pmc: PMC8447895
doi:
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
604-620Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Augustin, H. G., Kozian, D. H., & Johnson, R. C. (1994). Differentiation of endothelial cells: Analysis of the constitutive and activated endothelial cell phenotypes. BioEssays: news and reviews in molecular, cellular and developmental biology, 16, 901–906.
doi: 10.1002/bies.950161208
Loukas, M., Clarke, P., Tubbs, R. S., Kapos, T., & Trotz, M. (2008). The His family and their contributions to cardiology. International Journal of Cardiology, 123, 75–78.
pubmed: 17433467
doi: 10.1016/j.ijcard.2006.12.070
Luscher, T. F., & Barton, M. (1997). Biology of the endothelium. Clinical cardiology, 20, II-3–10.
doi: 10.1002/j.1932-8737.1997.tb00006.x
Jaffe, E. A. (1987). Cell biology of endothelial cells. Human Pathology, 18, 234–239.
pubmed: 3546072
doi: 10.1016/S0046-8177(87)80005-9
Godo, S., & Shimokawa, H. (2017). Endothelial functions. Arteriosclerosis, Thrombosis, and Vascular Biology, 37, e108–e114.
pubmed: 28835487
doi: 10.1161/ATVBAHA.117.309813
Michiels, C. (2003). Endothelial cell functions. Journal of Cellular Physiology, 196, 430–443.
pubmed: 12891700
doi: 10.1002/jcp.10333
Mombouli, J. V., & Vanhoutte, P. M. (1999). Endothelial dysfunction: From physiology to therapy. Journal of Molecular and Cellular Cardiology, 31, 61–74.
pubmed: 10072716
doi: 10.1006/jmcc.1998.0844
Davignon, J., & Ganz, P. (2004). Role of endothelial dysfunction in atherosclerosis. Circulation, 109, III27-32.
pubmed: 15198963
Moncada, S., & Higgs, E. A. (2006). The discovery of nitric oxide and its role in vascular biology. British Journal of Pharmacology. https://doi.org/10.1038/sj.bjp.0706458
doi: 10.1038/sj.bjp.0706458
pubmed: 16402104
pmcid: 1760731
Palmer, R. M., Ferrige, A. G., & Moncada, S. (1987). Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature, 327, 524–526.
pubmed: 3495737
doi: 10.1038/327524a0
Emoto, N., Vignon-Zellweger, N., Lopes, R. A., Cacioppo, J., Desbiens, L., Kamato, D., Leurgans, T., Moorhouse, R., Straube, J., Wurm, R., et al. (2014). 25 years of endothelin research: The next generation. Life sciences, 118, 77–86.
pubmed: 25238993
doi: 10.1016/j.lfs.2014.07.035
Galley, H. F., & Webster, N. R. (2004). Physiology of the endothelium. British Journal of Anaesth, 93, 105–113.
doi: 10.1093/bja/aeh163
Yamazaki, Y., & Kanekiyo, T. (2017). Blood-brain barrier dysfunction and the pathogenesis of Alzheimer’s disease. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms18091965
doi: 10.3390/ijms18091965
pubmed: 29137187
pmcid: 5713370
Booth, F. W., Roberts, C. K., & Laye, M. J. (2012). Lack of exercise is a major cause of chronic diseases. Comprehensive Physiology, 2, 1143–1211.
pubmed: 23798298
pmcid: 4241367
doi: 10.1002/cphy.c110025
Duvivier, B., Bolijn, J. E., Koster, A., Schalkwijk, C. G., Savelberg, H., & Schaper, N. C. (2018). Reducing sitting time versus adding exercise: Differential effects on biomarkers of endothelial dysfunction and metabolic risk. Scientific Reports. https://doi.org/10.1038/s41598-018-26616-w
doi: 10.1038/s41598-018-26616-w
pubmed: 29872225
pmcid: 5988819
Anderson, T. J., Uehata, A., Gerhard, M. D., Meredith, I. T., Knab, S., Delagrange, D., Lieberman, E. H., Ganz, P., Creager, M. A., Yeung, A. C., et al. (1995). Close relation of endothelial function in the human coronary and peripheral circulations. Journal of the American College of Cardiology, 26, 1235–1241.
pubmed: 7594037
doi: 10.1016/0735-1097(95)00327-4
Scicchitano, P., Cortese, F., Gesualdo, M., De Palo, M., Massari, F., Giordano, P., & Ciccone, M. M. (2019). The role of endothelial dysfunction and oxidative stress in cerebrovascular diseases. Free Radical Research, 53, 579–595.
pubmed: 31106620
doi: 10.1080/10715762.2019.1620939
Karoli, N. A., & Rebrov, A. P. (2019). Endothelial dysfunction in patients with chronic obstructive pulmonary disease in combination with coronary heart disease. Terapevticheskii Arkhiv, 91, 22–26.
pubmed: 31094454
doi: 10.26442/00403660.2019.03.000061
Brutsaert, D. L., Fransen, P., Andries, L. J., De Keulenaer, G. W., & Sys, S. U. (1998). Cardiac endothelium and myocardial function. Cardiovascular Research, 38, 281–290.
pubmed: 9709389
doi: 10.1016/S0008-6363(98)00044-3
Smiljic, S. (2017). The clinical significance of endocardial endothelial dysfunction. Medicina (Kaunas, Lithuania), 53, 295–302.
doi: 10.1016/j.medici.2017.08.003
Tang, D. H., Bai, S., Li, X. L., Yao, M., Gong, Y. J., Hou, Y. J., Li, J., & Yang, D. S. (2019). Improvement of microvascular endothelial dysfunction induced by exercise and diet is associated with microRNA-126 in obese adolescents. Microvascular Research, 123, 86–91.
doi: 10.1016/j.mvr.2018.10.009
Cecchi, F., Sgalambro, A., Baldi, M., Sotgia, B., Antoniucci, D., Camici, P. G., Sciagra, R., & Olivotto, I. (2009). Microvascular dysfunction, myocardial ischemia, and progression to heart failure in patients with hypertrophic cardiomyopathy. Journal of Cardiovascular Translational Research, 2, 452–461.
pubmed: 20560003
doi: 10.1007/s12265-009-9142-5
Brutsaert, D. L. (2003). Cardiac endothelial-myocardial signaling: Its role in cardiac growth, contractile performance, and rhythmicity. Physiological Reviews, 83, 59–115.
pubmed: 12506127
doi: 10.1152/physrev.00017.2002
Qiu, J., Li, J., & He, T. C. (2011). Endothelial cell damage induces a blood-alveolus barrier breakdown in the development of radiation-induced lung injury. Asia-Pacific Journal of Clinical Oncology, 7, 392–398.
pubmed: 22151990
doi: 10.1111/j.1743-7563.2011.01461.x
Good, R. B., Gilbane, A. J., Trinder, S. L., Denton, C. P., Coghlan, G., Abraham, D. J., & Holmes, A. M. (2015). Endothelial to mesenchymal transition contributes to endothelial dysfunction in pulmonary arterial hypertension. American Journal of Pathology, 185, 1850–1858.
pubmed: 25956031
doi: 10.1016/j.ajpath.2015.03.019
Graves, S. I., & Baker, D. J. (2020). Implicating endothelial cell senescence to dysfunction in the ageing and diseased brain. Basic & Clinical Pharmacology & Toxicology, 127, 102–110.
doi: 10.1111/bcpt.13403
Wardlaw, J. M., Smith, C., & Dichgans, M. (2019). Small vessel disease: Mechanisms and clinical implications. Lancet Neurology, 18, 684–696.
pubmed: 31097385
doi: 10.1016/S1474-4422(19)30079-1
Poggesi, A., Pasi, M., Pescini, F., Pantoni, L., & Inzitari, D. (2016). Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review. Journal of Cerebral Blood Flow and Metabolism, 36, 72–94.
pubmed: 26058695
pmcid: 4758546
doi: 10.1038/jcbfm.2015.116
Jourde-Chiche, N., Fakhouri, F., Dou, L., Bellien, J., Burtey, S., Frimat, M., Jarrot, P. A., Kaplanski, G., Le Quintrec, M., Pernin, V., et al. (2019). Endothelium structure and function in kidney health and disease. Nature Reviews Nephrology, 15, 87–108.
pubmed: 30607032
doi: 10.1038/s41581-018-0098-z
Jankauskas, S. S., Andrianova, N. V., Alieva, I. B., Prusov, A. N., Matsievsky, D. D., Zorova, L. D., Pevzner, I. B., Savchenko, E. S., Pirogov, Y. A., Silachev, D. N., et al. (2016). Dysfunction of kidney endothelium after ischemia/reperfusion and its prevention by mitochondria-targeted antioxidant. Biochemistry (Moscow), 81, 1538–1548.
doi: 10.1134/S0006297916120154
Malyszko, J. (2010). Mechanism of endothelial dysfunction in chronic kidney disease. Clinica Chimica Acta, 411, 1412–1420.
doi: 10.1016/j.cca.2010.06.019
Hammoutene, A., & Rautou, P. E. (2019). Role of liver sinusoidal endothelial cells in non-alcoholic fatty liver disease. Journal of Hepatology, 70, 1278–1291.
pubmed: 30797053
doi: 10.1016/j.jhep.2019.02.012
Rockey, D. C. (2015). Endothelial dysfunction in advanced liver disease. American Journal of the Medical Sciences, 349, 6–16.
pubmed: 25559279
doi: 10.1097/MAJ.0000000000000403
Poisson, J., Lemoinne, S., Boulanger, C., Durand, F., Moreau, R., Valla, D., & Rautou, P. E. (2017). Liver sinusoidal endothelial cells: Physiology and role in liver diseases. Journal of Hepatology, 66, 212–227.
pubmed: 27423426
doi: 10.1016/j.jhep.2016.07.009
Bernardo, B. C., Ooi, J. Y. Y., Weeks, K. L., Patterson, N. L., & McMullen, J. R. (2018). Understanding key mechanisms of exercise-induced cardiac protection to mitigate disease: Current knowledge and emerging concepts. Physiological Reviews, 98, 419–475.
pubmed: 29351515
doi: 10.1152/physrev.00043.2016
Rocha, B., Rodrigues, A. R., Tomada, I., Martins, M. J., Guimaraes, J. T., Gouveia, A. M., Almeida, H., & Neves, D. (2018). Energy restriction, exercise and atorvastatin treatment improve endothelial dysfunction and inhibit miRNA-155 in the erectile tissue of the aged rat. Nutrition & Metabolism. https://doi.org/10.1186/s12986-018-0265-z
La Favor, J. D., Anderson, E. J., Dawkins, J. T., Hickner, R. C., & Wingard, C. J. (2013). Exercise prevents Western diet-associated erectile dysfunction and coronary artery endothelial dysfunction: Response to acute apocynin and sepiapterin treatment. American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 305, R423–R434.
pubmed: 23761637
pmcid: 4839473
doi: 10.1152/ajpregu.00049.2013
Lee, S., Park, Y., & Zhang, C. (2011). Exercise training prevents coronary endothelial dysfunction in type 2 diabetic mice. American Journal of Biomedical Sciences, 3, 241–252.
pubmed: 22384308
pmcid: 3289260
doi: 10.5099/aj110400241
Pi, X., Xie, L., & Patterson, C. (2018). Emerging roles of vascular endothelium in metabolic homeostasis. Circulation Research, 123, 477–494.
pubmed: 30355249
pmcid: 6205216
doi: 10.1161/CIRCRESAHA.118.313237
Wong, B. W., Marsch, E., Treps, L., Baes, M., & Carmeliet, P. (2017). Endothelial cell metabolism in health and disease: Impact of hypoxia. EMBO Journal, 36, 2187–2203.
pubmed: 28637793
pmcid: 5538796
doi: 10.15252/embj.201696150
Eelen, G., de Zeeuw, P., Simons, M., & Carmeliet, P. (2015). Endothelial cell metabolism in normal and diseased vasculature. Circulation Research, 116, 1231–1244.
pubmed: 25814684
pmcid: 4380230
doi: 10.1161/CIRCRESAHA.116.302855
Cannon, M. S. (1984). A histochemical study of the metabolism of rat renal arteries and arterioles. Angiology, 35, 129–136.
pubmed: 6200011
doi: 10.1177/000331978403500301
Cook, B. H., Granger, H. J., & Taylor, A. E. (1977). Metabolism of coronary arteries and arterioles: A histochemical study. Microvascular Research, 14, 145–159.
pubmed: 144839
doi: 10.1016/0026-2862(77)90014-0
Byts' Iu, V., and Ataman, A. V. (1989). Energy metabolism in arteries and veins in modelling epinephrine damage to the vascular wall. Patol Fiziol Eksp Ter, 63–66.
Sarelius, I. H., Cohen, K. D., & Murrant, C. L. (2000). Role for capillaries in coupling blood flow with metabolism. Clinical and Experimental Pharmacology and Physiology, 27, 826–829.
pubmed: 11022977
doi: 10.1046/j.1440-1681.2000.03340.x
Menghini, R., Casagrande, V., Iuliani, G., Rizza, S., Mavilio, M., Cardellini, M., & Federici, M. (2020). Metabolic aspects of cardiovascular diseases: Is FoxO1 a player or a target? International Journal of Biochemistry and Cell Biology, 118, 105659.
pubmed: 31765819
doi: 10.1016/j.biocel.2019.105659
Wilhelm, K., Happel, K., Eelen, G., Schoors, S., Oellerich, M. F., Lim, R., Zimmermann, B., Aspalter, I. M., Franco, C. A., Boettger, T., et al. (2016). FOXO1 couples metabolic activity and growth state in the vascular endothelium. Nature, 529, 216–220.
pubmed: 26735015
pmcid: 5380221
doi: 10.1038/nature16498
Hariharan, N., Maejima, Y., Nakae, J., Paik, J., Depinho, R. A., & Sadoshima, J. (2010). Deacetylation of FoxO by Sirt1 plays an essential role in mediating starvation-induced autophagy in cardiac myocytes. Circulation Research, 107, 1470–1482.
pubmed: 20947830
pmcid: 3011986
doi: 10.1161/CIRCRESAHA.110.227371
Rudnicki, M., Abdifarkosh, G., Nwadozi, E., Ramos, S. V., Makki, A., Sepa-Kishi, D. M., Ceddia, R. B., Perry, C. G., Roudier, E., & Haas, T. L. (2018). Endothelial-specific FoxO1 depletion prevents obesity-related disorders by increasing vascular metabolism and growth. elife. https://doi.org/10.7554/eLife.39780 .
Celermajer, D. S., Sorensen, K. E., Gooch, V. M., Spiegelhalter, D. J., Miller, O. I., Sullivan, I. D., Lloyd, J. K., & Deanfield, J. E. (1992). Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet, 340, 1111–1115.
pubmed: 1359209
doi: 10.1016/0140-6736(92)93147-F
Takase, B., Uehata, A., Fujioka, T., Kondo, T., Nishioka, T., Isojima, K., Satomura, K., Ohsuzu, F., & Kurita, A. (2001). Endothelial dysfunction and decreased exercise tolerance in interferon-alpha therapy in chronic hepatitis C: Relation between exercise hyperemia and endothelial function. Clinical Cardiology, 24, 286–290.
pubmed: 11303695
doi: 10.1002/clc.4960240406
Huang, P. H., Leu, H. B., Chen, J. W., Cheng, C. M., Huang, C. Y., Tuan, T. C., Ding, P. Y. A., & Lin, S. J. (2004). Usefulness of attenuated heart rate recovery immediately after exercise to predict endothelial dysfunction in patients with suspected coronary artery disease. American Journal of Cardiology, 93, 10–13.
pubmed: 14697458
doi: 10.1016/j.amjcard.2003.09.004
Kuvin, J. T., Patel, A. R., Sliney, K. A., Pandian, N. G., Sheffy, J., Schnall, R. P., Karas, R. H., & Udelson, J. E. (2003). Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. American Heart Journal, 146, 168–174.
pubmed: 12851627
doi: 10.1016/S0002-8703(03)00094-2
Boos, C. J., Balakrishnan, B., & Lip, G. Y. H. (2008). The effects of exercise stress testing on soluble E-selectin, von Willebrand factor, and circulating endothelial cells as indices of endothelial damage/dysfunction. Annals of Medicine, 40, 66–73.
pubmed: 17934907
doi: 10.1080/07853890701652833
Boos, C. J., Lip, G. Y., & Blann, A. D. (2006). Circulating endothelial cells in cardiovascular disease. Journal of the American College of Cardiology, 48, 1538–1547.
pubmed: 17045885
doi: 10.1016/j.jacc.2006.02.078
Wang, L., Wang, J., Cretoiu, D., Li, G., & Xiao, J. (2020). Exercise-mediated regulation of autophagy in the cardiovascular system. Journal of Sport and Health Science, 9, 203–210.
pubmed: 32444145
doi: 10.1016/j.jshs.2019.10.001
Luan, X., Tian, X. Y., Zhang, H. X., Huang, R., Li, N., Chen, P. J., & Wang, R. (2019). Exercise as a prescription for patients with various diseases. Journal of Sport and Health Science, 8, 422–441.
pubmed: 31534817
pmcid: 6742679
doi: 10.1016/j.jshs.2019.04.002
Gielen, S., Schuler, G., & Hambrecht, R. (2001). Exercise training in coronary artery disease and coronary vasomotion. Circulation, 103, E1-6. https://doi.org/10.1161/01.cir.103.1.e1
doi: 10.1161/01.cir.103.1.e1
pubmed: 11136704
De Keulenaer, G. W., Segers, V. F. M., Zannad, F., & Brutsaert, D. L. (2017). The future of pleiotropic therapy in heart failure. Lessons from the benefits of exercise training on endothelial function. European Journal of Heart Failure, 19, 603–614.
pubmed: 28105791
doi: 10.1002/ejhf.735
Wang, R. W., Tian, H. L., Guo, D. D., Tian, Q. Q., Yao, T., & Kong, X. X. (2020). Impacts of exercise intervention on various diseases in rats. Journal of Sport and Health Science, 9, 211–227.
pubmed: 32444146
doi: 10.1016/j.jshs.2019.09.008
Downey, R. M., Liao, P. Z., Millson, E. C., Quyyumi, A. A., Sher, S., & Park, J. (2017). Endothelial dysfunction correlates with exaggerated exercise pressor response during whole body maximal exercise in chronic kidney disease. American Journal of Physiology-Renal Physiology, 312, F917–F924.
pubmed: 28274927
pmcid: 5451552
doi: 10.1152/ajprenal.00603.2016
La Favor, J. D., Dubis, G. S., Yan, H., White, J. D., Nelson, M. A., Anderson, E. J., & Hickner, R. C. (2016). Microvascular endothelial dysfunction in sedentary, obese humans is mediated by NADPH oxidase: Influence of exercise training. Arteriosclerosis, Thrombosis, and Vascular Biology, 36, 2412–2420.
pubmed: 27765769
pmcid: 5123754
doi: 10.1161/ATVBAHA.116.308339
Schuler, G., Adams, V., & Goto, Y. (2013). Role of exercise in the prevention of cardiovascular disease: Results, mechanisms, and new perspectives. European Heart Journal, 34, 1790–1799.
pubmed: 23569199
doi: 10.1093/eurheartj/eht111
Seo, D. Y., Ko, J. R., Jang, J. E., Kim, T. N., Youm, J. B., Kwak, H. B., Bae, J. H., Kim, A. H., Ko, K. S., Rhee, B. D., et al. (2019). Exercise as a potential therapeutic target for diabetic cardiomyopathy: Insight into the underlying mechanisms. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms20246284
doi: 10.3390/ijms20246284
pubmed: 31847135
pmcid: 6940971
Vona, M., Codeluppi, G. M., Iannino, T., Ferrari, E., Bogousslavsky, J., & von Segesser, L. K. (2009). Effects of different types of exercise training followed by detraining on endothelium-dependent dilation in patients with recent myocardial infarction. Circulation, 119, 1601–1608.
pubmed: 19289636
doi: 10.1161/CIRCULATIONAHA.108.821736
Gevaert, A. B., Beckers, P. J., Van Craenenbroeck, A. H., Lemmens, K., Van De Heyning, C. M., Heidbuchel, H., Vrints, C. J., & Van Craenenbroeck, E. M. (2019). Endothelial dysfunction and cellular repair in heart failure with preserved ejection fraction: Response to a single maximal exercise bout. European Journal of Heart Failure, 21, 125–127.
pubmed: 30468294
doi: 10.1002/ejhf.1339
Djohan, A. H., Sia, C. H., Lee, P. S., & Poh, K. K. (2018). Endothelial progenitor cells in heart failure: An authentic expectation for potential future use and a lack of universal definition. Journal of Cardiovascular Translational Research, 11, 393–402.
pubmed: 29777508
doi: 10.1007/s12265-018-9810-4
Asahara, T., Murohara, T., Sullivan, A., Silver, M., van der Zee, R., Li, T., Witzenbichler, B., Schatteman, G., & Isner, J. M. (1997). Isolation of putative progenitor endothelial cells for angiogenesis. Science, 275, 964–967.
pubmed: 9020076
doi: 10.1126/science.275.5302.964
Kaushik, K., & Das, A. (2019). Endothelial progenitor cell therapy for chronic wound tissue regeneration. Cytotherapy, 21, 1137–1150.
pubmed: 31668487
doi: 10.1016/j.jcyt.2019.09.002
Qiao, J., Qi, K., Chu, P., Mi, H., Yang, N., Yao, H., Xia, Y., Li, Z., Xu, K., & Zeng, L. (2015). Infusion of endothelial progenitor cells ameliorates liver injury in mice after haematopoietic stem cell transplantation. Liver International, 35, 2611–2620.
pubmed: 25872801
doi: 10.1111/liv.12849
Zhao, Q., Liu, Z., Wang, Z., Yang, C., Liu, J., & Lu, J. (2007). Effect of prepro-calcitonin gene-related peptide-expressing endothelial progenitor cells on pulmonary hypertension. Annals of Thoracic Surgery, 84, 544–552.
pubmed: 17643632
doi: 10.1016/j.athoracsur.2007.03.067
Ming, G. F., Tang, Y. J., Hu, K., Chen, Y., Huang, W. H., & Xiao, J. (2016). Visfatin attenuates the ox-LDL-induced senescence of endothelial progenitor cells by upregulating SIRT1 expression through the PI3K/Akt/ERK pathway. International Journal of Molecular Medicine, 38, 643–649.
pubmed: 27277186
doi: 10.3892/ijmm.2016.2633
Subramaniyam, V., Waller, E. K., Murrow, J. R., Manatunga, A., Lonial, S., Kasirajan, K., Sutcliffe, D., Harris, W., Taylor, W. R., Alexander, R. W., et al. (2009). Bone marrow mobilization with granulocyte macrophage colony-stimulating factor improves endothelial dysfunction and exercise capacity in patients with peripheral arterial disease. American Heart Journal, 158, 53–60.
Recchioni, R., Marcheselli, F., Antonicelli, R., Lazzarini, R., Mensa, E., Testa, R., Procopio, A. D., & Olivieri, F. (2016). Physical activity and progenitor cell-mediated endothelial repair in chronic heart failure: Is there a role for epigenetics? Mechanisms of Ageing and Development, 159, 71–80.
pubmed: 27015708
doi: 10.1016/j.mad.2016.03.008
Sandri, M., Adams, V., Gielen, S., Linke, A., Lenk, K., Krankel, N., Lenz, D., Erbs, S., Scheinert, D., Mohr, F. W., et al. (2005). Effects of exercise and ischemia on mobilization and functional activation of blood-derived progenitor cells in patients with ischemic syndromes: Results of 3 randomized studies. Circulation, 111, 3391–3399.
pubmed: 15956121
doi: 10.1161/CIRCULATIONAHA.104.527135
Steiner, S., Niessner, A., Ziegler, S., Richter, B., Seidinger, D., Pleiner, J., Penka, M., Wolzt, M., Huber, K., Wojta, J., et al. (2005). Endurance training increases the number of endothelial progenitor cells in patients with cardiovascular risk and coronary artery disease. Atherosclerosis, 181, 305–310.
pubmed: 16039284
doi: 10.1016/j.atherosclerosis.2005.01.006
Schlager, O., Giurgea, A., Schuhfried, O., Seidinger, D., Hammer, A., Groger, M., Fialka-Moser, V., Gschwandtner, M., Koppensteiner, R., & Steiner, S. (2011). Exercise training increases endothelial progenitor cells and decreases asymmetric dimethylarginine in peripheral arterial disease: A randomized controlled trial. Atherosclerosis, 217, 240–248.
pubmed: 21481871
doi: 10.1016/j.atherosclerosis.2011.03.018
Brehm, M., Picard, F., Ebner, P., Turan, G., Bolke, E., Kostering, M., Schuller, P., Fleissner, T., Ilousis, D., Augusta, K., et al. (2009). Effects of exercise training on mobilization and functional activity of blood-derived progenitor cells in patients with acute myocardial infarction. European Journal of Medical Research, 14, 393–405.
pubmed: 19748858
pmcid: 3351971
doi: 10.1186/2047-783X-14-9-393
Bei, Y., Wang, L., Ding, R., Che, L., Fan, Z., Gao, W., Liang, Q., Lin, S., Liu, S., Lu, X., et al. (2021). Animal exercise studies in cardiovascular research: Current knowledge and optimal design-A position paper of the Committee on Cardiac Rehabilitation Chinese, Medical Doctors’ Association. Journal of Sport and Health Science. https://doi.org/10.1016/j.jshs.2021.08.002
doi: 10.1016/j.jshs.2021.08.002
pubmed: 34454088
pmcid: 8724626
Hambrecht, R., Wolf, A., Gielen, S., Linke, A., Hofer, J., Erbs, S., Schoene, N., & Schuler, G. (2000). Effect of exercise on coronary endothelial function in patients with coronary artery disease. New England Journal of Medicine, 342, 454–460.
pubmed: 10675425
doi: 10.1056/NEJM200002173420702
Luk, T. H., Dai, Y. L., Siu, C. W., Yiu, K. H., Chan, H. T., Lee, S. W., Li, S. W., Fong, B., Wong, W. K., Tam, S., et al. (2012). Effect of exercise training on vascular endothelial function in patients with stable coronary artery disease: A randomized controlled trial. European Journal of Preventive Cardiology, 19, 830–839.
pubmed: 21724681
doi: 10.1177/1741826711415679
Edwards, D. G., Schofield, R. S., Lennon, S. L., Pierce, G. L., Nichols, W. W., & Braith, R. W. (2004). Effect of exercise training on endothelial function in men with coronary artery disease. American Journal of Cardiology, 93, 617–620.
pubmed: 14996592
doi: 10.1016/j.amjcard.2003.11.032
Gokce, N., Vita, J. A., Bader, D. S., Sherman, D. L., Hunter, L. M., Holbrook, M., O’Malley, C., Keaney, J. F., Jr., & Balady, G. J. (2002). Effect of exercise on upper and lower extremity endothelial function in patients with coronary artery disease. American Journal of Cardiology, 90, 124–127.
pubmed: 12106840
doi: 10.1016/S0002-9149(02)02433-5
Adams, V., Linke, A., Krankel, N., Erbs, S., Gielen, S., Mobius-Winkler, S., Gummert, J. F., Mohr, F. W., Schuler, G., & Hambrecht, R. (2005). Impact of regular physical activity on the NAD(P)H oxidase and angiotensin receptor system in patients with coronary artery disease. Circulation, 111, 555–562.
pubmed: 15699275
doi: 10.1161/01.CIR.0000154560.88933.7E
Hambrecht, R., Adams, V., Erbs, S., Linke, A., Krankel, N., Shu, Y., Baither, Y., Gielen, S., Thiele, H., Gummert, J. F., et al. (2003). Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase. Circulation, 107, 3152–3158.
pubmed: 12810615
doi: 10.1161/01.CIR.0000074229.93804.5C
Hosokawa, S., Hiasa, Y., Takahashi, T., & Itoh, S. (2003). Effect of regular exercise on coronary endothelial function in patients with recent myocardial infarction. Circulation Journal, 67, 221–224.
pubmed: 12604870
doi: 10.1253/circj.67.221
Belardinelli, R., Mucaj, A., Lacalaprice, F., Solenghi, M., Seddaiu, G., Principi, F., Tiano, L., & Littarru, G. P. (2006). Coenzyme Q10 and exercise training in chronic heart failure. European Heart Journal, 27, 2675–2681.
pubmed: 16882678
doi: 10.1093/eurheartj/ehl158
Adamopoulos, S., Parissis, J., Kroupis, C., Georgiadis, M., Karatzas, D., Karavolias, G., Koniavitou, K., Coats, A. J., & Kremastinos, D. T. (2001). Physical training reduces peripheral markers of inflammation in patients with chronic heart failure. European Heart Journal, 22, 791–797.
pubmed: 11350112
doi: 10.1053/euhj.2000.2285
Mancini, D. M., Walter, G., Reichek, N., Lenkinski, R., McCully, K. K., Mullen, J. L., & Wilson, J. R. (1992). Contribution of skeletal muscle atrophy to exercise intolerance and altered muscle metabolism in heart failure. Circulation, 85, 1364–1373.
pubmed: 1555280
doi: 10.1161/01.CIR.85.4.1364
Hwang, M. H., & Kim, S. (2014). Type 2 diabetes: Endothelial dysfunction and exercise. Journal of Exercise Nutrition & Biochemistry, 18, 239–247.
doi: 10.5717/jenb.2014.18.3.239
Liese, A. D., Ma, X. G., Maahs, D. M., & Trilk, J. L. (2013). Physical activity, sedentary behaviors, physical fitness, and their relation to health outcomes in youth with type 1 and type 2 diabetes: A review of the epidemiologic literature. Journal of Sport and Health Science, 2, 21–38.
doi: 10.1016/j.jshs.2012.10.005
Leung, F. P., Yung, L. M., Laher, I., Yao, X., Chen, Z. Y., & Huang, Y. (2008). Exercise, vascular wall and cardiovascular diseases: An update (Part 1). Sports Medicine, 38, 1009–1024.
pubmed: 19026018
doi: 10.2165/00007256-200838120-00005
Yung, L. M., Laher, I., Yao, X., Chen, Z. Y., Huang, Y., & Leung, F. P. (2009). Exercise, vascular wall and cardiovascular diseases: An update (part 2). Sports Medicine, 39, 45–63.
pubmed: 19093695
doi: 10.2165/00007256-200939010-00004
Sixt, S., Beer, S., Bluher, M., Korff, N., Peschel, T., Sonnabend, M., Teupser, D., Thiery, J., Adams, V., Schuler, G., et al. (2010). Long- but not short-term multifactorial intervention with focus on exercise training improves coronary endothelial dysfunction in diabetes mellitus type 2 and coronary artery disease. European Heart Journal, 31, 112–119.
pubmed: 19793768
doi: 10.1093/eurheartj/ehp398
Cheang, W. S., Wong, W. T., Zhao, L., Xu, J., Wang, L., Lau, C. W., Chen, Z. Y., Ma, R. C., Xu, A., Wang, N., et al. (2017). PPARdelta is required for exercise to attenuate endoplasmic reticulum stress and endothelial dysfunction in diabetic mice. Diabetes, 66, 519–528.
pubmed: 27856609
doi: 10.2337/db15-1657
Dong, Y., Zhang, M., Wang, S., Liang, B., Zhao, Z., Liu, C., Wu, M., Choi, H. C., Lyons, T. J., & Zou, M. H. (2010). Activation of AMP-activated protein kinase inhibits oxidized LDL-triggered endoplasmic reticulum stress in vivo. Diabetes, 59, 1386–1396.
pubmed: 20299472
pmcid: 2874699
doi: 10.2337/db09-1637
Davis, B. J., Xie, Z., Viollet, B., & Zou, M. H. (2006). Activation of the AMP-activated kinase by antidiabetes drug metformin stimulates nitric oxide synthesis in vivo by promoting the association of heat shock protein 90 and endothelial nitric oxide synthase. Diabetes, 55, 496–505.
pubmed: 16443786
doi: 10.2337/diabetes.55.02.06.db05-1064
Enkhjargal, B., Godo, S., Sawada, A., Suvd, N., Saito, H., Noda, K., Satoh, K., & Shimokawa, H. (2014). Endothelial AMP-activated protein kinase regulates blood pressure and coronary flow responses through hyperpolarization mechanism in mice. Arteriosclerosis, Thrombosis, And Vascular Biology, 34, 1505–1513.
pubmed: 24855056
doi: 10.1161/ATVBAHA.114.303735
Cheang, W. S., Tian, X. Y., Wong, W. T., Lau, C. W., Lee, S. S., Chen, Z. Y., Yao, X., Wang, N., & Huang, Y. (2014). Metformin protects endothelial function in diet-induced obese mice by inhibition of endoplasmic reticulum stress through 5’ adenosine monophosphate-activated protein kinase-peroxisome proliferator-activated receptor delta pathway. Arteriosclerosis, Thrombosis, and Vascular Biology, 34, 830–836.
pubmed: 24482374
doi: 10.1161/ATVBAHA.113.301938
Lee, C. H., Olson, P., Hevener, A., Mehl, I., Chong, L. W., Olefsky, J. M., Gonzalez, F. J., Ham, J., Kang, H., Peters, J. M., et al. (2006). PPARdelta regulates glucose metabolism and insulin sensitivity. Proceedings of the National Academy of Sciences, 103, 3444–3449.
doi: 10.1073/pnas.0511253103
Narkar, V. A., Downes, M., Yu, R. T., Embler, E., Wang, Y. X., Banayo, E., Mihaylova, M. M., Nelson, M. C., Zou, Y., Juguilon, H., et al. (2008). AMPK and PPARdelta agonists are exercise mimetics. Cell, 134, 405–415.
pubmed: 18674809
pmcid: 2706130
doi: 10.1016/j.cell.2008.06.051
Lauer, T., Heiss, C., Balzer, J., Kehmeier, E., Mangold, S., Leyendecker, T., Rottler, J., Meyer, C., Merx, M. W., Kelm, M., et al. (2008). Age-dependent endothelial dysfunction is associated with failure to increase plasma nitrite in response to exercise. Basic Research in Cardiology, 103, 291–297.
pubmed: 18347836
doi: 10.1007/s00395-008-0714-3
Margaritis, M., Sanna, F., & Antoniades, C. (2017). Statins and oxidative stress in the cardiovascular system. Current Pharmaceutical Design. https://doi.org/10.2174/1381612823666170926130338
doi: 10.2174/1381612823666170926130338
pubmed: 28950824
Park, J. H., Iemitsu, M., Maeda, S., Kitajima, A., Nosaka, T., & Omi, N. (2008). Voluntary running exercise attenuates the progression of endothelial dysfunction and arterial calcification in ovariectomized rats. Acta Physiologiae Plantarum, 193, 47–55.
doi: 10.1111/j.1748-1716.2007.01799.x
Maeda, S., Tanabe, T., Miyauchi, T., Otsuki, T., Sugawara, J., Iemitsu, M., Kuno, S., Ajisaka, R., Yamaguchi, I., & Matsuda, M. (2003). Aerobic exercise training reduces plasma endothelin-1 concentration in older women. Journal of Applied Physiology, 95, 336–341.
pubmed: 12611765
doi: 10.1152/japplphysiol.01016.2002
Maeda, S., Tanabe, T., Otsuki, T., Sugawara, J., Iemitsu, M., Miyauchi, T., Kuno, S., Ajisaka, R., & Matsuda, M. (2004). Moderate regular exercise increases basal production of nitric oxide in elderly women. Hypertension Research: Official Journal of the Japanese Society of Hypertension, 27, 947–953.
doi: 10.1291/hypres.27.947
Harvey, P. J., Picton, P. E., Su, W. S., Morris, B. L., Notarius, C. F., & Floras, J. S. (2005). Exercise as an alternative to oral estrogen for amelioration of endothelial dysfunction in postmenopausal women. American Heart Journal, 149, 291–297.
pubmed: 15846267
doi: 10.1016/j.ahj.2004.08.036
Xu, M., Duan, Y., & Xiao, J. (2019). Exercise improves the function of endothelial cells by MicroRNA. Journal of Cardiovascular Translational Research, 12, 391–393.
pubmed: 30604308
doi: 10.1007/s12265-018-9855-4
Wang, L., Lv, Y., Li, G., & Xiao, J. (2018). MicroRNAs in heart and circulation during physical exercise. Journal of Sport and Health Science, 7, 433–441.
pubmed: 30450252
pmcid: 6226555
doi: 10.1016/j.jshs.2018.09.008
Zhang, J., Zhao, F., Yu, X., Lu, X., & Zheng, G. (2015). MicroRNA-155 modulates the proliferation of vascular smooth muscle cells by targeting endothelial nitric oxide synthase. International Journal of Molecular Sciences, 35, 1708–1714.
Sun, H. X., Zeng, D. Y., Li, R. T., Pang, R. P., Yang, H., Hu, Y. L., Zhang, Q., Jiang, Y., Huang, L. Y., Tang, Y. B., et al. (2012). Essential role of microRNA-155 in regulating endothelium-dependent vasorelaxation by targeting endothelial nitric oxide synthase. Hypertension, 60, 1407–1414.
pubmed: 23108656
doi: 10.1161/HYPERTENSIONAHA.112.197301
Tang, S. T., Wang, F., Shao, M., Wang, Y., & Zhu, H. Q. (2017). MicroRNA-126 suppresses inflammation in endothelial cells under hyperglycemic condition by targeting HMGB1. Vascular Pharmacology, 88, 48–55.
pubmed: 27993686
doi: 10.1016/j.vph.2016.12.002
van Balkom, B. W., de Jong, O. G., Smits, M., Brummelman, J., den Ouden, K., de Bree, P. M., van Eijndhoven, M. A., Pegtel, D. M., Stoorvogel, W., Wurdinger, T., et al. (2013). Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells. Blood, 121, 3997–4006.
pubmed: 23532734
doi: 10.1182/blood-2013-02-478925
Yang, B. Y., Li, S. Z., Zhu, J., Huang, S. M., Zhang, A. H., Jia, Z. J., Ding, G. X., & Zhang, Y. (2020). miR-214 protects against uric acid-induced endothelial cell apoptosis. Frontiers in Medicine (Lausanne). https://doi.org/10.3389/fmed.2020.00411
doi: 10.3389/fmed.2020.00411
pmcid: 7729194
Li, S., Xie, Y., Yang, B., Huang, S., Zhang, Y., Jia, Z., Ding, G., & Zhang, A. (2020). MicroRNA-214 targets COX-2 to antagonize indoxyl sulfate (IS)-induced endothelial cell apoptosis. Apoptosis, 25, 92–104.
pubmed: 31820187
doi: 10.1007/s10495-019-01582-4
Wang, S., Liao, J. W., Huang, J. H., Yin, H. G., Yang, W. Y., & Hu, M. (2018). miR-214 and miR-126 were associated with restoration of endothelial function in obesity after exercise and dietary intervention. Journal of Applied Biomedicine, 16, 34–39.
doi: 10.1016/j.jab.2017.10.003
Chamorro-Jorganes, A., Araldi, E., Penalva, L. O., Sandhu, D., Fernandez-Hernando, C., & Suarez, Y. (2011). MicroRNA-16 and microRNA-424 regulate cell-autonomous angiogenic functions in endothelial cells via targeting vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1. Arteriosclerosis, Thrombosis, and Vascular Biology, 31, 2595–2606.
pubmed: 21885851
pmcid: 3226744
doi: 10.1161/ATVBAHA.111.236521
Fernandes, T., Casaes, L., Soci, U., Silveira, A., Gomes, J., Barretti, D., Roque, F., & Oliveira, E. (2018). Exercise training restores the cardiac microrna-16 levels preventing microvascular rarefaction in obese Zucker rats. Obesity Facts, 11, 15–24.
pubmed: 29402872
pmcid: 5869535
doi: 10.1159/000454835
Cai, Y., Xie, K. L., Zheng, F., & Liu, S. X. (2018). Aerobic exercise prevents insulin resistance through the regulation of miR-492/resistin axis in aortic endothelium. Journal of Cardiovascular Translational Research, 11, 450–458.
pubmed: 30232730
doi: 10.1007/s12265-018-9828-7
Meng, S., Cao, J., Zhang, X., Fan, Y., Fang, L., Wang, C., Lv, Z., Fu, D., & Li, Y. (2013). Downregulation of microRNA-130a contributes to endothelial progenitor cell dysfunction in diabetic patients via its target Runx3. PLoS ONE. https://doi.org/10.1371/journal.pone.0068611
doi: 10.1371/journal.pone.0068611
pubmed: 24391711
pmcid: 3876984
Olivieri, F., Lazzarini, R., Recchioni, R., Marcheselli, F., Rippo, M. R., Di Nuzzo, S., Albertini, M. C., Graciotti, L., Babini, L., Mariotti, S., et al. (2013). MiR-146a as marker of senescence-associated pro-inflammatory status in cells involved in vascular remodelling. Age, 35, 1157–1172.
pubmed: 22692818
doi: 10.1007/s11357-012-9440-8
Cirilli, I., Silvestri, S., Marcheggiani, F., Olivieri, F., Galeazzi, R., Antonicelli, R., Recchioni, R., Marcheselli, F., Bacchetti, T., Tiano, L., et al. (2019). Three months monitored metabolic fitness modulates cardiovascular risk factors in diabetic patients. Diabetes & Metabolism Journal, 43, 893–897.
doi: 10.4093/dmj.2018.0254
Kureishi, Y., Luo, Z., Shiojima, I., Bialik, A., Fulton, D., Lefer, D. J., Sessa, W. C., & Walsh, K. (2000). The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nature Medicine, 6, 1004–1010.
pubmed: 10973320
pmcid: 2828689
doi: 10.1038/79510
Gong, X., Ma, Y., Ruan, Y., Fu, G., & Wu, S. (2014). Long-term atorvastatin improves age-related endothelial dysfunction by ameliorating oxidative stress and normalizing eNOS/iNOS imbalance in rat aorta. Experimental Gerontology, 52, 9–17.
pubmed: 24463049
doi: 10.1016/j.exger.2014.01.015
Farquharson, C. A., Butler, R., Hill, A., Belch, J. J., & Struthers, A. D. (2002). Allopurinol improves endothelial dysfunction in chronic heart failure. Circulation, 106, 221–226.
pubmed: 12105162
doi: 10.1161/01.CIR.0000022140.61460.1D
Wyss, C. A., Koepfli, P., Namdar, M., Siegrist, P. T., Luscher, T. F., Camici, P. G., & Kaufmann, P. A. (2005). Tetrahydrobiopterin restores impaired coronary microvascular dysfunction in hypercholesterolaemia. European Journal of Nuclear Medicine and Molecular Imaging, 32, 84–91.
pubmed: 15290118
doi: 10.1007/s00259-004-1621-y
Melandri, G., Semprini, F., Cervi, V., Candiotti, N., Palazzini, E., Branzi, A., & Magnani, B. (1993). Benefit of adding low molecular weight heparin to the conventional treatment of stable angina pectoris. A double-blind, randomized, placebo-controlled trial. Circulation, 88, 2517–2523.
pubmed: 8252662
doi: 10.1161/01.CIR.88.6.2517
Rosengart, T. K., Lee, L. Y., Patel, S. R., Sanborn, T. A., Parikh, M., Bergman, G. W., Hachamovitch, R., Szulc, M., Kligfield, P. D., Okin, P. M., et al. (1999). Angiogenesis gene therapy: Phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease. Circulation, 100, 468–474.
pubmed: 10430759
doi: 10.1161/01.CIR.100.5.468
Rajagopalan, S., Shah, M., Luciano, A., Crystal, R., & Nabel, E. G. (2001). Adenovirus-mediated gene transfer of VEGF(121) improves lower-extremity endothelial function and flow reserve. Circulation, 104, 753–755.
pubmed: 11502697
doi: 10.1161/hc3201.095192