{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:07:09Z","timestamp":1791558429509,"version":"4.3.4"},"reference-count":154,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T00:00:00Z","timestamp":1554076800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["vb.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,4,1]]},"abstract":"<jats:p>\n                    Skeletal muscle relies on an ingenious network of blood vessels, which ensures optimal oxygen and nutrient supply. An increase in muscle vascularization is an early adaptive event to exercise training, but the cellular and molecular mechanisms underlying exercise-induced blood vessel formation are not completely clear. In this review, we provide a concise overview on how exercise-induced alterations in muscle metabolism can evoke metabolic changes in endothelial cells (ECs) that drive muscle angiogenesis. In skeletal muscle, angiogenesis can occur via sprouting and splitting angiogenesis and is dependent on vascular endothelial growth factor (VEGF) signaling. In the resting muscle, VEGF levels are controlled by the estrogen-related receptor \u03b3 (ERR\u03b3). Upon exercise, the transcriptional coactivator peroxisome-proliferator-activated receptor-\u03b3 coactivator-1\u03b1 (PGC1\u03b1) orchestrates several adaptations to endurance exercise within muscle fibers and simultaneously promotes transcriptional activation of\n                    <jats:italic>Vegf<\/jats:italic>\n                    expression and increased muscle capillary density. While ECs are highly glycolytic and change their metabolism during sprouting angiogenesis in development and disease, a similar role for EC metabolism in exercise-induced angiogenesis in skeletal muscle remains to be elucidated. Nonetheless, recent studies have illustrated the importance of endothelial hydrogen sulfide and sirtuin 1 (SIRT1) activity for exercise-induced angiogenesis, suggesting that EC metabolic reprogramming may be fundamental in this process. We hypothesize that the exercise-induced angiogenic response can also be modulated by metabolic crosstalk between muscle and the endothelium. Defining the underlying molecular mechanisms responsible for skeletal muscle angiogenesis in response to exercise will yield valuable insight into metabolic regulation as well as the determinants of exercise performance.\n                  <\/jats:p>","DOI":"10.1530\/vb-19-0008","type":"journal-article","created":{"date-parts":[[2019,3,11]],"date-time":"2019-03-11T12:07:24Z","timestamp":1552306044000},"page":"H1-H8","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-12","source":"Crossref","is-referenced-by-count":66,"title":["Metabolic regulation of exercise-induced angiogenesis"],"prefix":"10.1530","volume":"1","author":[{"given":"Tatiane","family":"Gorski","sequence":"first","affiliation":[{"name":"Department of Health Sciences and Technology, Laboratory of Exercise and Health, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrien","family":"De Bock","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Technology, Laboratory of Exercise and Health, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref41","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1046\/j.1365-201x.2000.00706.x","article-title":"Coupling of muscle metabolism and muscle blood flow in capillary units during contraction","volume":"168","year":"2000","journal-title":"Acta Physiologica Scandinavica"},{"key":"ref1511","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s10456-012-9282-0","article-title":"Lactate stimulates angiogenesis and accelerates the healing of superficial and ischemic wounds in mice","volume":"15","year":"2012","journal-title":"Angiogenesis"},{"key":"ref891","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1161\/CIRCULATIONAHA.109.881888","article-title":"Exercise rehabilitation in peripheral artery disease: functional impact and mechanisms of benefits","volume":"123","year":"2011","journal-title":"Circulation"},{"key":"ref581","doi-asserted-by":"crossref","first-page":"4543","DOI":"10.1172\/JCI120912","article-title":"Endothelial pyruvate kinase M2 maintains vascular integrity","volume":"128","year":"2018","journal-title":"Journal of Clinical Investigation"},{"key":"ref871","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1113\/jphysiol.1977.sp011975","article-title":"Capillary supply of the quadriceps femoris muscle of man: adaptive response to exercise","volume":"270","year":"1977","journal-title":"Journal of Physiology"},{"key":"ref171","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/nature05571","article-title":"Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis","volume":"445","year":"2007","journal-title":"Nature"},{"key":"ref531","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1073\/pnas.0808801106","article-title":"PGC-1 is coupled to HIF-1 -dependent gene expression by increasing mitochondrial oxygen consumption in skeletal muscle cells","volume":"106","year":"2009","journal-title":"PNAS"},{"key":"ref771","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.2337\/diab.30.12.1000","article-title":"The effect of insulin on the disposal of intravenous glucose. 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