Activation of TRPV4 Increases Neovascularization of Rat Prefabricated Flaps

Abstract

Activation of TRPV4 using 4αPDD can significantly increase the survival of prefabricated flaps via neovascularization inducement, possibly through VEGF secretion enhancement. TRPV4 serves as a potential therapeutic neovascularization target in prefabricated flaps.

Prefabrication—a Vascularized Skin Flap Using an Arteriovenous LoopPrefabricated Flap With Arteriovenous Loop

“…Cx43,19 a gap junction protein minimally expressed at physiological flow, regulates vascular endothelial cell migration and initiates angiogenic signaling pathways. Besides, recent findings indicate that transient receptor potential cation channel, subfamily V, member 4 (TRPV4), a Ca 2+ channel sensitive to FSS, regulates the Ca 2+ influx to dilate the vessel wall in response to higher FSS and activates the growth and remodeling of collateral arteries, thereby increasing capillary density 20,21. Through genetic testing, Henn detected deregulation of miRNA as well as the overexpression of angiopoietin, oxygenation-associated genes, vascular growth factors, and Cx43 in human arteriovenous loops, providing genetic support that elevated FSS triggers pro-angiogenic signaling pathways in venous tissue and thus induce vascularization 22…”

“…Besides, recent findings indicate that transient receptor potential cation channel, subfamily V, member 4 (TRPV4), a Ca 2+ channel sensitive to FSS, regulates the Ca 2+ influx to dilate the vessel wall in response to higher FSS and activates the growth and remodeling of collateral arteries, thereby increasing capillary density. 20,21 Through genetic testing, Henn detected deregulation of miRNA as well as the overexpression of angiopoietin, oxygenation-associated genes, vascular growth factors, and Cx43 in human arteriovenous loops, providing genetic support that elevated FSS triggers proangiogenic signaling pathways in venous tissue and thus induce vascularization. 22 Unlike earlier prefabricated flaps with arteriovenous loops, a long segment of venous graft was interposed between the artery and vein in the present experiment.…”

Transient receptor potential vanilloid (TRPV) channels: Basal properties and physiological potential

“…4α-PDD treatment elicits the dilation of mesenteric arteries in aged rats by increasing intracellular Ca 2+ levels (Du et al 2016). In rat prefabricated skin flaps, 4α-PDD increases the survival of prefabricated flaps through neovascularization induction via vascular endothelial growth factor (VEGF) secretion (Bae et al 2018). Glial cells are abundant in the CNS and play key roles in the regulation of neuronal activity, vascular function, and gliotransmitter release.…”

Augmentation of Perforator Flap Blood Supply with Vascular Supercharge or Flap Prefabrication: Evaluation in a Rat Model

“…Twenty-one male Sprague-Dawley rats (300 to 400 g) were randomized with a random number table followed by ear clipping to three groups of seven animals each, namely, group A (single perforator flap), group B (supercharged perforator flap), and group C (prefabricated perforator flap). The animal models for perforator flap and flap prefabrication used in this experiment were established in two stages, as described previously 17,18 (Fig. 1).…”