Vascular endothelial growth factor
Vascular endothelial growth factor (VEGF) is the primary driver of angiogenesis in skin: the process through which new blood vessels form, and through which existing vessels are maintained during active tissue remodelling. It is produced by keratinocytes, dermal fibroblasts, and dermal papilla cells, stored in platelet alpha granules, and released by multiple professional treatments. But VEGF’s role in skin biology extends well beyond “improved blood supply”: without adequate VEGF-driven perifollicular angiogenesis, hair follicles cannot sustain active growth; without pericyte recruitment through coordinated PDGF-BB signalling, VEGF-driven new vessels remain structurally unstable; and in photodamaged skin, VEGF dysregulation contributes to the persistent redness and vascular fragility that clients present alongside texture and collagen concerns.
Vascular endothelial growth factor is a family of secreted glycoproteins – the primary isoforms in human skin being VEGF-A, VEGF-C, and placental growth factor (PlGF) – of which VEGF-A is the dominant pro-angiogenic signal in wound healing and tissue maintenance. [4] VEGF-A signals through two receptor tyrosine kinases on vascular endothelial cells (VEGFR-1 and VEGFR-2) with VEGFR-2 being the primary angiogenic signalling receptor. When VEGF-A binds VEGFR-2, it triggers endothelial cell proliferation, migration, and tube formation, the three cellular steps required to build a new vessel.
| Component | Role | Clinical Impact |
|---|---|---|
| VEGF-A | Dominant pro-angiogenic ligand. | The primary “start” signal for new vessel growth. |
| VEGFR-2 | Main signalling receptor on Endothelium. | Triggers cell migration and “sprouting.” |
| HIF-1α | Hypoxia-inducible transcription factor. | The “sensor” that tells cells to produce VEGF when oxygen is low. |
VEGF is produced constitutively in normal skin by keratinocytes, dermal fibroblasts, and dermal papilla cells, and its expression is upregulated rapidly in response to tissue injury, hypoxia, and growth factor signalling including FGF-2. [3] It is also stored in platelet alpha granules and released acutely on platelet activation, making it part of the immediate growth factor response at any site of tissue disruption, whether from injury, treatment, or controlled wounding.
Angiogenesis and the Vessel Maturation Problem
VEGF initiates angiogenesis but does not complete it alone. This distinction is clinically important. VEGF drives endothelial cell proliferation and tube formation; but newly formed endothelial tubes are immature, structurally unstable, and prone to leakage without adequate pericyte coverage. As described in the PDGF entity, it is PDGF-BB – secreted by the endothelial cells themselves as vessels form – that recruits pericytes to the abluminal vessel wall. [6] Pericytes then deposit the vascular basement membrane – collagen IV, laminin, fibronectin, perlecan – that stabilises vessel diameter, prevents haemorrhage, and establishes the durable capillary structure that tissue remodelling depends on.
Without this VEGF–PDGF coordination, VEGF-driven angiogenesis produces a network of leaky, unstable vessels – the pattern seen in tumour vasculature and in pathological skin conditions including rosacea, where vessel formation outpaces maturation. [3] iPRF delivers both VEGF and PDGF-BB simultaneously from the same platelet preparation, providing both the angiogenic stimulus and the pericyte recruitment signal in the same fibrin-released payload – a coordination that neither growth factor achieves in isolation.
The Angiogenic “Handshake” (VEGF + PDGF)
| Signal | Stage | Biological Action | Resulting Vessel State |
|---|---|---|---|
| VEGF | Initiation | Endothelial proliferation/tube formation. | Immature: Leaky, unstable, dilated. |
| PDGF-BB | Maturation | Pericyte recruitment & basement membrane. | Mature: Stable, functional, durable. |
| Combined | iPRF Payload | Coordinated Construction. | Optimised: Healthy microcirculation. |
VEGF in the Hair Follicle: Perifollicular Angiogenesis
One of the most specific and well-characterised roles for VEGF in skin biology is in hair follicle cycling. Dermal papilla cells express and secrete VEGF during anagen (the active growth phase) driving expansion of the perifollicular capillary plexus that supplies the metabolically demanding growing follicle with nutrients, oxygen, and systemic signals including hormones and additional growth factors. [3] This perifollicular vasculature is not static, it expands during anagen and regresses during catagen and telogen, contracting alongside the follicle as it enters its resting phase.
VEGF expression in dermal papilla cells is therefore both a product of active DPC function and a requirement for sustaining the anagen phase. When DPC function is compromised – by DHT in androgenetic alopecia, by glucocorticoids in stress-driven shedding, or by advancing miniaturisation – VEGF secretion falls, the perifollicular vasculature contracts, and the follicle receives progressively less vascular support alongside progressively less GAS6 and FGF-7 paracrine signalling. These deficits reinforce each other: a less vascularised follicle is a less metabolically supported follicle, which is a follicle that is less capable of sustaining the energy-intensive anagen growth phase.
VEGF, the HSPG Reservoir, and ECM-Bound Signalling
VEGF does not only signal in free soluble form. Like FGF-2, VEGF binds to heparan sulphate proteoglycans (particularly perlecan) in the ECM, creating a reservoir of growth factor that is protected from degradation and released in controlled quantities by heparanase and MMPs. [5] This HSPG-bound VEGF pool is part of the same ECM growth factor reservoir described in the HSPG entity: a slow-release, locally available source of angiogenic signal that is progressively depleted in aged, UV-damaged, and MMP-overactive skin.
The connection runs deeper: perlecan – one of the vascular basement membrane components deposited by pericytes during vessel maturation – is both a VEGF reservoir and a structural component of the vessel wall itself. PDGF-BB-driven pericyte recruitment therefore contributes not only to vessel stability but to rebuilding the very HSPG matrix that stores and releases both VEGF and FGF-2 for subsequent tissue maintenance. This is one of the more elegant examples in skin biology of a repair mechanism that also restores the long-term maintenance infrastructure.
VEGF in Photodamaged and Aged Skin
Photodamaged skin presents a VEGF signalling picture that is dysregulated rather than simply depleted. Chronic UV exposure stimulates VEGF expression in keratinocytes, contributing to the persistent telangiectasia, redness, and vascular fragility that clients present alongside collagen and texture concerns. [2] This UV-driven VEGF upregulation is not beneficial angiogenesis but disorganised vessel proliferation without the corresponding PDGF-BB-driven pericyte recruitment and maturation. The result is a superficial vascular network of structurally immature, pericyte-poor vessels, visible as diffuse redness and easy flushing rather than the organised, adequately supported vasculature of healthy skin.
In aged skin without significant photodamage, the picture shifts toward VEGF depletion: less constitutive VEGF production from fibroblasts and keratinocytes, less HSPG-bound VEGF reservoir, and a progressively less vascular dermis with reduced nutrient and oxygen delivery to both fibroblasts and hair follicles. Both excess and deficit of VEGF signalling produce clinically visible outcomes, which is one reason that treatments delivering VEGF into the appropriate tissue context (rather than as a general systemic stimulus) produce better outcomes than broadly pro-angiogenic approaches.
Clinical Application
VEGF is relevant across more of the Creative Touch treatment portfolio than is usually acknowledged, and in more specific ways than “improves blood supply.” Understanding what VEGF is actually doing in each context makes the treatment logic more precise and the client conversation more substantive.
iPRF and PRP: the coordinated delivery advantage
iPRF and PRP deliver VEGF and PDGF-BB together from the same platelet preparation, which matters precisely because vessel maturation requires both signals in coordination. VEGF without PDGF-BB drives endothelial tube formation that remains immature and leaky; PDGF-BB ensures pericytes are recruited to stabilise what VEGF has built. [6] The fibrin scaffold of iPRF releases both growth factors over days rather than as a single bolus, maintaining the coordinated signalling environment that vessel maturation requires rather than delivering a brief pulse that dissipates before pericyte recruitment can complete.
For scalp iPRF treatments specifically, this coordination is directly relevant to the perifollicular capillary network. VEGF drives its expansion during anagen; PDGF-BB matures and stabilises the vessels that expansion produces. A well-vascularised, structurally stable perifollicular network is the vascular foundation that DPC signalling, FGF-7 secretion, and GAS6-driven HFSC activation all depend on for adequate metabolic support.
Polynucleotides: VEGF upregulation through A2A receptor activation
Polynucleotides have a direct and well-evidenced relationship to VEGF that goes beyond environmental support. PDRN’s primary pro-angiogenic mechanism operates through adenosine A2A receptor activation, which upregulates endogenous VEGF production in tissue, stimulating angiogenesis and wound healing through the tissue’s own VEGF secretion rather than delivering exogenous VEGF. [1] This makes polynucleotides genuinely pro-angiogenic in their own right, not as a VEGF delivery vehicle but as a VEGF production stimulus. In tissue where endogenous VEGF production has declined with age or photodamage, polynucleotides restore part of the constitutive angiogenic signal that normal skin generates.
The sequencing implication is that polynucleotides used as a first-stage treatment improve not only the ECM environment but the vascular environment into which subsequent iPRF VEGF delivery arrives. The tissue is already upregulating its own VEGF production when iPRF adds its exogenous payload.
RF microneedling and thulium laser: controlled hypoxia as a VEGF stimulus
RF microneedling and thulium fractional laser both create microscopic zones of thermal injury in which local oxygen tension drops transiently, and hypoxia is one of the most potent physiological VEGF inducers, operating through HIF-1α (hypoxia-inducible factor 1-alpha) transcriptional upregulation of VEGF gene expression. [4] The controlled wound environment of these treatments therefore generates an endogenous VEGF stimulus through the same hypoxic mechanism that drives VEGF production in healing wounds, contributing to the neovascularisation component of the skin renewal these treatments achieve.
Applying iPRF post-procedure delivers exogenous VEGF into a tissue that is already upregulating endogenous VEGF through hypoxic signalling, amplifying the angiogenic stimulus at the moment it is most biologically active and supporting the vessel maturation process through the coordinated PDGF-BB payload.
Red light therapy: modulation rather than stimulation
LED red and near-infrared therapy has a nuanced relationship with VEGF. At therapeutic doses, photobiomodulation modulates the inflammatory and oxidative environment in which VEGF signalling operates, reducing excessive pro-inflammatory cytokine activity that can dysregulate angiogenesis, rather than directly stimulating VEGF production. [7] In photodamaged skin where UV-driven VEGF overexpression has produced disorganised, pericyte-poor vessels, the anti-inflammatory modulation of LED therapy may contribute to normalising rather than amplifying an angiogenic signal that is already excessive. This makes LED therapy an appropriate post-laser adjunct not just for comfort but for supporting organised rather than disorganised vascular remodelling.
Rosacea: when VEGF dysregulation is the presenting concern
For clients presenting with rosacea or persistent diffuse redness, the VEGF picture is different from the angiogenic deficit of aged skin: it is dysregulated excess rather than depletion, with UV-driven and inflammatory VEGF upregulation producing structurally immature vessels without adequate pericyte coverage. The treatment logic here is not to add more VEGF but to reduce the inflammatory signals driving its overproduction whilst supporting the pericyte recruitment and vessel maturation processes that would stabilise the existing vascular network. Polynucleotides’ anti-inflammatory and VEGF-moderating effects alongside their A2A angiogenic action make them a genuinely rational first-line choice in this context, restoring vascular regulation rather than adding angiogenic stimulus to tissue that already has too much of it.
Treatment Interaction with VEGF
| Treatment | VEGF Mechanism | Best Use Case |
|---|---|---|
| iPRF | Direct Delivery | Rapid restoration of hair follicles and “vascular deserts.” |
| Polynucleotides | A2A Stimulus | Restoring endogenous “rhythm” in aged or Rosacea-prone skin. |
| RFM / Laser | Hypoxic Trigger | Forcing a “reboot” of the repair cascade via HIF−1α. |
| Red Light (LED) | Modulation | Calming disorganised, pericyte-poor “UV-redness.” |
References
Baek A, Kim Y, Lee JW, et al. (2018). Effect of Polydeoxyribonucleotide on Angiogenesis and Wound Healing in an In Vitro Model of Osteoarthritis. Cell Transplant, 27(11), 1623-1633 . doi.org/10.1177/0963689718804130
Hernández-Bule ML, Naharro-Rodríguez J, Bacci S, et al. (2024). Unlocking the Power of Light on the Skin: A Comprehensive Review on Photobiomodulation. Int J Mol Sci, 25(8) . doi.org/10.3390/ijms25084483
Mehta A, Motavaf M, Raza D, et al. (2025). Revolutionary Approaches to Hair Regrowth: Follicle Neogenesis, Wnt/ß-Catenin Signaling, and Emerging Therapies. Cells, 14(11) . doi.org/10.3390/cells14110779
Park JW, Hwang SR, Yoon IS (2017). Advanced Growth Factor Delivery Systems in Wound Management and Skin Regeneration. Molecules, 22(8) . doi.org/10.3390/molecules22081259
Slominski AT, Manna PR, Tuckey RC (2014). Cutaneous glucocorticosteroidogenesis: securing local homeostasis and the skin integrity. Exp Dermatol, 23(6), 369-374 . doi.org/10.1111/exd.12376
Stratman AN, Schwindt AE, Malotte KM, et al. (2010). Endothelial-derived PDGF-BB and HB-EGF coordinately regulate pericyte recruitment during vasculogenic tube assembly and stabilization. Blood, 116(22), 4720-30 . doi.org/10.1182/blood-2010-05-286872
Ucci S, Caradonna E, Aliberti A, et al. (2025). Photobiomodulation in fibroblasts: from light to healing through molecular pathways, omics and artificial intelligence. Front Bioeng Biotechnol, 13, 1675619 . doi.org/10.3389/fbioe.2025.1675619
Also Known As
- VEGF
Biological Relationships
Biological Interactions
- Stimulates Anagen Evidence: VEGF expression in DPCs drives perifollicular vascularisation during anagen; vasculature expands during anagen, regresses during catagen/telogen. Entity text; Yano et al. 2001 JCI PMC199257.
- Stimulates Hair follicle Evidence: VEGF drives expansion of perifollicular capillary plexus supplying growing hair follicle; transgenic VEGF overexpression increases follicle size. PMC12153676; Yano 2001 PMC199257.
- Stimulates Platelet-derived growth factor Evidence: VEGF-initiated endothelial tube formation prompts endothelial cells to secrete PDGF-BB for pericyte recruitment; VEGF initiates cascade leading to PDGF-BB production. PMC2996127.
- Stimulates Rosacea Evidence: LL-37 drives VEGF expression, promoting angiogenesis and the telangiectasia of erythematotelangiectatic rosacea.
- Stimulates Tissue regeneration Evidence: VEGF drives neovascularisation as an active component of tissue regeneration; RF/laser-induced hypoxia generates VEGF stimulus via HIF-1alpha. Entity text; PMC6152378.
- Interacts with Platelet-derived growth factor Evidence: VEGF-PDGF coordinated angiogenesis: VEGF drives endothelial tube formation; PDGF-BB recruits pericytes to stabilise immature vessels. Entity text; PMC2996127.
- Associated disease Androgenetic alopecia Evidence: VEGF secretion falls in DHT-compromised DPCs in AGA; VEGF serum levels correlate with hair count (r=0.9965) in AGA treatment. Entity text; Kawen 2025 DOI 10.15570/actaapa.2025.5.
- Associated disease Telogen effluvium Evidence: VEGF deficiency impairs perifollicular vasculature; reduced VEGF secretion from compromised DPCs contributes to telogen effluvium. PMC12153676.
- Affects Dermis Evidence: VEGF drives angiogenesis maintaining capillary network essential for dermal fibroblast nutrition; VEGF depletion produces progressively less vascular dermis. PMC11049838.
Influenced By
- this Stimulated by Heparan sulfate proteoglycans
- this Stimulated by Microneedling Evidence: VEGF expression increases during wound healing proliferative phase initiated by microneedling, driving angiogenesis and new capillary formation in treated dermis. PMC11993440.
- this Stimulated by Polynucleotides Evidence: PDRN increases VEGF mRNA and protein, stimulates angiogenesis, increases CD31 immunostaining (new capillary formation) via A2AR activation. PMC6299200, Cell Transplantation 2018.
- this Interacts with Platelet-derived growth factor Evidence: VEGF-PDGF coordinated angiogenesis: PDGF-BB recruits pericytes to stabilise VEGF-built endothelial tubes. Entity text; PMC2996127.
- this Produced by Dermal Papilla Evidence: Dermal papilla cells express VEGF during the anagen phase, driving perifollicular angiogenesis – the formation and maintenance of the capillary network
- this Produced by Hair follicle Evidence: Entity text: VEGF upregulated in ORS keratinocytes as follicle enters anagen; this drives perifollicular angiogenesis. Yano et al. (2001) J Clin Invest 107(4):409. PMC199257
- this Produced by Platelet-rich plasma therapy Evidence: VEGF stored in platelet alpha granules released on platelet activation in PRP/iPRF preparations. PMC5329835; PMC4487960.
- this Component of Heparan sulfate proteoglycans Evidence: HSPGs (particularly perlecan) store VEGF as ECM-bound reservoir for controlled slow-release; VEGF binds HSPG in dermis. PMC4046116.
- this Affected by LED therapy Evidence: LED red/NIR therapy modulates VEGF signalling environment by reducing pro-inflammatory cytokines dysregulating angiogenesis; particularly relevant in rosacea. Entity text; PMC12571845.
- this Required by Hair follicle Evidence: Entity text: blocking VEGF-mediated angiogenesis directly impairs hair growth; perifollicular VEGF is an active requirement for anagen sustenance. PMC199257
- this Required by Tissue regeneration Evidence: VEGF-driven angiogenesis is required for tissue regeneration: new vasculature delivers oxygen and nutrients; VEGF from platelets and macrophages initiates vessel sprouting during the proliferative phase (PMC7371992).
Learn More
This topic is discussed in 3 articles:
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Discover the detailed science behind PRP and iPRF therapies. Learn how growth factors, platelets, and cellular mechanisms drive hair restoration and skin rejuvenation at a molecular level.
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Discover how plasma treatments offer a safe, effective, and minimally invasive way to achieve tighter skin, reduce wrinkles, improve acne, and remove skin tags.