C Uchida1, E Nwadozi1, A Hasanee1, S Olenich2, I M Olfert2, T L Haas1. 1. School of Kinesiology and Health Science, Angiogenesis Research Group, York University, Toronto, ON, Canada. 2. Division of Exercise Physiology & Center for Cardiovascular and Respiratory Sciences, West Virginia University, Morgantown, WV, USA.
Abstract
AIM: The source of vascular endothelial growth factor-A (VEGF-A) may influence vascular function. Exercise-induced vascular growth has been attributed to elevated metabolic demand and to increased blood flow, involving the production of VEGF-A by skeletal muscle and by endothelial cells respectively. We hypothesized that muscle-derived VEGF-A is not required for vascular adaptations to blood flow in skeletal muscle, as this remodelling stimulus originates within the capillary. METHODS: Myocyte-specific VEGF-A (mVEGF(-/-) ) deleted mice were treated for 7-21 days with the vasodilator prazosin to produce a sustained increase in skeletal muscle blood flow. RESULTS: Capillary number increased in the extensor digitorum longus (EDL) muscle in response to prazosin in wild type but not mVEGF(-/-) mice. Prazosin increased the number of smooth muscle actin-positive blood vessels in the EDL of wild-type but not mVEGF(-/-) mice. The average size of smooth muscle actin-positive blood vessels also was smaller in knockout mice after prazosin treatment. In response to prazosin treatment, VEGF-A mRNA was elevated within the EDL of wild-type but not mVEGF(-/-) mice. Ex vivo incubation of wild-type EDL with a nitric oxide donor increased VEGF-A mRNA. Likewise, we demonstrated that nitric oxide donor treatment of cultured myoblasts stimulated an increase in VEGF-A mRNA and protein. CONCLUSION: These results suggest a link through which flow-mediated endothelial-derived signals may promote myocyte production of VEGF-A. In turn, myocyte-derived VEGF-A is required for appropriate flow-mediated microvascular remodelling. This highlights the importance of the local environment and paracrine interactions in the regulation of tissue perfusion.
AIM: The source of vascular endothelial growth factor-A (VEGF-A) may influence vascular function. Exercise-induced vascular growth has been attributed to elevated metabolic demand and to increased blood flow, involving the production of VEGF-A by skeletal muscle and by endothelial cells respectively. We hypothesized that muscle-derived VEGF-A is not required for vascular adaptations to blood flow in skeletal muscle, as this remodelling stimulus originates within the capillary. METHODS: Myocyte-specific VEGF-A (mVEGF(-/-) ) deleted mice were treated for 7-21 days with the vasodilator prazosin to produce a sustained increase in skeletal muscle blood flow. RESULTS: Capillary number increased in the extensor digitorum longus (EDL) muscle in response to prazosin in wild type but not mVEGF(-/-)mice. Prazosin increased the number of smooth muscle actin-positive blood vessels in the EDL of wild-type but not mVEGF(-/-)mice. The average size of smooth muscle actin-positive blood vessels also was smaller in knockout mice after prazosin treatment. In response to prazosin treatment, VEGF-A mRNA was elevated within the EDL of wild-type but not mVEGF(-/-)mice. Ex vivo incubation of wild-type EDL with a nitric oxidedonor increased VEGF-A mRNA. Likewise, we demonstrated that nitric oxidedonor treatment of cultured myoblasts stimulated an increase in VEGF-A mRNA and protein. CONCLUSION: These results suggest a link through which flow-mediated endothelial-derived signals may promote myocyte production of VEGF-A. In turn, myocyte-derived VEGF-A is required for appropriate flow-mediated microvascular remodelling. This highlights the importance of the local environment and paracrine interactions in the regulation of tissue perfusion.
Authors: Kikumi D Ono-Moore; I Mark Olfert; Jennifer M Rutkowsky; Sree V Chintapalli; Brandon J Willis; Michael L Blackburn; D Keith Williams; Juliana O'Reilly; Todd Tolentino; K C Kent Lloyd; Sean H Adams Journal: Am J Physiol Endocrinol Metab Date: 2021-05-10 Impact factor: 5.900
Authors: Erin R Mandel; Emily C Dunford; Anastassia Trifonova; Ghoncheh Abdifarkosh; Trevor Teich; Michael C Riddell; Tara L Haas Journal: PLoS One Date: 2016-11-18 Impact factor: 3.240