GO:0061043 regulation of vascular wound healing: Angiogenesis Control, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0061043 (regulation of vascular wound healing) is a biological process that modulates the rate, frequency, or extent of new blood vessel formation from pre-existing vessels during restoration of damaged vasculature.
• The process is orchestrated by a balance of pro-angiogenic and anti-angiogenic signals, including chemokines, microRNAs, catecholamines, and reactive oxygen species.
• Endothelial cells, pericytes, and inflammatory cells are key cellular players; their crosstalk determines whether healing proceeds or becomes chronic.
• Dysregulation of vascular wound healing underlies diabetic ulcers, chronic wounds, and tumor progression, making it a therapeutic target.
• Key molecular regulators include microRNA-26a, OTUD1, connexin 43, and catecholamine signaling pathways.
• CRISPR-based knockout, knock-in, and overexpression models enable causal dissection of these regulators in endothelial and pericyte populations.
Description
Regulation of vascular wound healing (GO:0061043) is the biological process that controls the rate, frequency, or extent of blood vessel formation when new vessels emerge from pre-existing vessels and contribute to restoring integrity to damaged vasculature. This process is essential for delivering oxygen and nutrients to injured tissue, removing debris, and supporting the formation of new matrix during repair. Because it sits at the intersection of angiogenesis and wound repair, its dysregulation is implicated in both impaired healing (e.g., diabetic ulcers) and pathological angiogenesis (e.g., tumor growth). Researchers study GO:0061043 to identify molecular switches that can be therapeutically modulated to accelerate healing or normalize aberrant vessel growth. The term encompasses signaling by chemokines, microRNAs, catecholamines, and reactive oxygen species, as well as cellular crosstalk between endothelial cells, pericytes, and immune cells. Understanding its mechanistic basis is therefore critical for developing targeted interventions in regenerative medicine and oncology.
regulation of vascular wound healing At A Glance
| GO ID | GO:0061043 |
|---|---|
| GO term | regulation of vascular wound healing |
| Ontology | biological_process |
| Synonym | none |
| Major function | Modulates the rate, frequency, or extent of new blood vessel formation from pre-existing vessels during restoration of damaged vasculature |
| Cellular players | Endothelial cells, pericytes, inflammatory cells, and their secreted factors |
| Key signaling molecules | Chemokines, microRNA-26a, catecholamines, connexin 43, reactive oxygen species, OTUD1 |
| Related processes | Angiogenesis, wound repair, vascular remodeling, inflammation resolution |
| Disease relevance | Diabetic wound healing impairment, chronic ulcers, tumor angiogenesis, and therapy resistance |
What Is GO:0061043?
In our own words, GO:0061043 describes any process that adjusts the speed, frequency, or extent of blood vessel formation from pre-existing vessels during the series of events that restore integrity to damaged vasculature. It is not the wound healing process itself, but the regulatory layer that modulates angiogenesis specifically within the context of vascular repair.
Why Is regulation of vascular wound healing Important in Cell Biology?
GO:0061043 is important because it governs the vascular component of tissue repair, a process that determines whether wounds heal or become chronic. In diabetes, impaired regulation of vascular wound healing leads to delayed ulcer healing and increased morbidity. In cancer, the same regulatory pathways can be hijacked to support tumor angiogenesis and therapy resistance. Thus, understanding GO:0061043 provides a mechanistic handle for therapeutic modulation in both regenerative medicine and oncology.
• Controls oxygen and nutrient delivery to injured tissue during repair.
• Dysregulation causes chronic wounds in diabetes and aging.
• Pericyte-endothelial crosstalk is a key regulatory node in cutaneous wound healing.
• Chemokine gradients direct immune cell recruitment and angiogenesis.
• MicroRNA-26a modulates impaired angiogenesis in diabetic wounds.
• Catecholamines influence angiogenesis in cutaneous wound healing.
• Connexin 43 and ROS signaling regulate endothelial cell survival during repair.
• OTUD1 delays wound healing by affecting endothelial function and angiogenesis.
• Tumor progression and therapy resistance depend on angiocrine and pericrine signaling.
• CRISPR models enable causal testing of candidate regulators in vivo and in vitro.
What Happens During regulation of vascular wound healing?
Initiation of the angiogenic response
In simple terms: When tissue is injured, nearby blood vessels start sprouting new branches to bring oxygen and nutrients.
Upon vascular injury, pro-angiogenic factors such as chemokines are released to initiate sprouting from pre-existing vessels. This early phase involves endothelial cell activation, basement membrane degradation, and tip cell selection, all modulated by regulatory signals that set the rate and extent of the response.
Endothelial cell proliferation and migration
In simple terms: Endothelial cells multiply and move to form new vessel tubes.
Regulation of vascular wound healing controls endothelial cell proliferation and directed migration. MicroRNA-26a has been shown to regulate impaired angiogenesis in diabetic dermal wound healing, affecting endothelial function. Catecholamines also modulate angiogenesis in cutaneous wound healing, influencing the balance between proliferation and quiescence.
Pericyte recruitment and vessel stabilization
In simple terms: Support cells called pericytes wrap around new vessels to make them stable.
Pericyte-mediated regulation of angiogenesis is critical during cutaneous wound healing, as shown in adult zebrafish models. Pericytes provide paracrine signals that stabilize nascent vessels and regulate endothelial survival, a process that is dysregulated in cancer and chronic wounds.
Resolution and remodeling
In simple terms: Once the wound is repaired, the new vessels are pruned and remodeled.
After tissue integrity is restored, regulatory mechanisms shift toward vessel maturation and pruning. Reactive oxygen species and connexin 43 signaling influence endothelial cell fate during this phase, with excessive ROS leading to pyroptosis and impaired healing. OTUD1 has been shown to delay wound healing by regulating endothelial function and angiogenesis, highlighting the importance of timely resolution.
Key Genes Involved in GO:0061043 regulation of vascular wound healing
The following genes and proteins are experimentally implicated in the regulation of vascular wound healing (GO:0061043).
| Gene | Major Role | Research Relevance |
|---|---|---|
| MIR26A | MicroRNA regulating angiogenesis | Impaired angiogenesis in diabetic dermal wound healing |
| OTUD1 | Deubiquitinase affecting endothelial function | Delays wound healing in diabetic mice |
| GJA1 (Connexin 43) | Gap junction protein regulating ROS and pyroptosis | Bioglass promotes wound healing via Cx43/ROS pathway |
| ADRB2 | Beta-2 adrenergic receptor mediating catecholamine effects | Catecholamines regulate angiogenesis in cutaneous wound healing |
| CXCL12 | Chemokine recruiting endothelial progenitor cells | Chemokine role in wound healing |
| CCL2 | Chemokine mediating monocyte recruitment | Chemokine role in wound healing |
| VEGFA | Major pro-angiogenic growth factor | Central to wound angiogenesis |
| PDGFB | Pericyte recruitment factor | Pericyte-mediated regulation of angiogenesis |
| ANGPT1 | Vessel stabilization factor | Pericyte-endothelial crosstalk |
| ANGPT2 | Vessel destabilization factor | Angiogenesis regulation |
| TGFB1 | Regulates endothelial and pericyte behavior | Wound repair signaling |
| HIF1A | Hypoxia-inducible factor driving angiogenesis | Wound healing response |
| NOS3 | Endothelial nitric oxide synthase | Vascular wound healing regulation |
| MMP9 | Matrix metalloproteinase for ECM remodeling | Wound repair and angiogenesis |
| TIMP1 | Inhibitor of MMPs | ECM remodeling balance |
| CDH5 | Endothelial adherens junction protein | Vessel integrity during healing |
| PECAM1 | Endothelial cell adhesion molecule | Angiogenesis quantification |
How Is regulation of vascular wound healing Regulated?
Regulation of vascular wound healing is controlled by a network of signaling pathways. MicroRNA-26a acts as a negative regulator of impaired angiogenesis in diabetic wounds. Catecholamines, via adrenergic receptors, modulate angiogenesis in cutaneous wound healing. Chemokines establish gradients that direct both inflammatory and endothelial cell recruitment. Reactive oxygen species and connexin 43 signaling determine endothelial cell survival versus pyroptosis. OTUD1, a deubiquitinase, delays wound healing by regulating endothelial function and angiogenesis. Pericytes provide paracrine signals that stabilize vessels and regulate endothelial behavior.
regulation of vascular wound healing and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| MIR26A | Diabetic wound healing impairment | Diabetic mouse model with miR-26a knockout or overexpression |
| OTUD1 | Diabetic wound healing delay | OTUD1 knockout mice in streptozotocin-induced diabetes |
| GJA1 | Impaired wound healing via ROS | Cx43 knockout or point-mutant endothelial cells |
| ADRB2 | Catecholamine-modulated angiogenesis | Adrb2 knockout mice in cutaneous wound models |
| VEGFA | Angiogenesis in cancer and wound healing | Inducible endothelial-specific Vegfa knockout |
Diabetic wound healing impairment
Diabetes impairs regulation of vascular wound healing, leading to chronic ulcers. MicroRNA-26a dysregulation contributes to impaired angiogenesis in diabetic dermal wounds. OTUD1 delays wound healing by affecting endothelial function and angiogenesis in diabetic mice. These findings suggest that targeting these regulators could improve healing outcomes.
Cancer and therapy resistance
Angiocrine and pericrine signaling, which are central to GO:0061043, also drive cancer progression and therapy resistance. Tumors hijack vascular wound healing programs to support growth and evade anti-angiogenic therapies. Understanding the regulatory nodes may reveal new targets for combination therapy.
Chronic inflammation and impaired repair
Chemokine-mediated regulation of vascular wound healing is critical for resolving inflammation and promoting repair. Dysregulated chemokine signaling can lead to persistent inflammation and impaired vessel formation, as seen in chronic wounds.
From regulation of vascular wound healing-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate endothelial sprouting during wound healing? | Endothelial-specific knockout (e.g., Cdh5-Cre; X fl/fl) |
| Does a point mutation in gene Y alter its regulatory function? | Knock-in of point mutant via CRISPR |
| Does overexpression of gene Z accelerate wound healing? | Transgenic overexpression or viral delivery |
| Is gene W required in pericytes for vessel stabilization? | Pericyte-specific knockout (e.g., Pdgfrb-Cre) |
| Does a microRNA mimic/inhibitor affect angiogenesis? | miR-26a mimic/inhibitor in diabetic wound models |
| Does a deubiquitinase regulate endothelial function? | OTUD1 knockout or overexpression in endothelial cells |
How to Study the regulation of vascular wound healing Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Cutaneous wound healing assay | Rate of wound closure and vascular density | In vivo assessment of GO:0061043 regulators |
| Tube formation assay | Endothelial cell network formation | In vitro angiogenesis |
| Immunofluorescence | Vessel density and pericyte coverage | Tissue analysis of wound healing |
| Western blot | Protein expression and phosphorylation | Signaling pathway validation |
| qPCR | mRNA and microRNA levels | Gene expression profiling |
| Luciferase reporter | MicroRNA target validation | Mechanistic studies |
| Zebrafish live imaging | Dynamic pericyte-endothelial interactions | Developmental and wound healing studies |
| ROS detection assay | Reactive oxygen species levels | Endothelial pyroptosis assessment |
In vivo wound healing models
Cutaneous wound healing models in mice, zebrafish, or other organisms allow assessment of vascular wound healing regulation. Zebrafish are particularly useful for live imaging of pericyte-mediated angiogenesis. Diabetic mouse models (e.g., streptozotocin-induced) reveal impaired healing phenotypes.
Endothelial cell functional assays
In vitro assays such as tube formation, spheroid sprouting, and migration measure endothelial cell responses under regulatory perturbations. These assays can be combined with knockout or overexpression of candidate genes.
Molecular signaling analysis
Western blotting, qPCR, and reporter assays quantify pathway activation. For example, connexin 43 and ROS levels are measured to assess endothelial pyroptosis. MicroRNA target validation uses luciferase reporters.
Imaging and histology
Immunofluorescence for endothelial markers (CD31, CDH5) and pericyte markers (PDGFRB) quantifies vessel density and pericyte coverage in wound tissue. Live imaging in zebrafish enables dynamic tracking of vascular wound healing.
How CRISPR Can Be Used to Study GO:0061043 regulation of vascular wound healing
Knockout
CRISPR knockout of candidate genes (e.g., OTUD1, GJA1) in endothelial cells or mice enables loss-of-function studies to determine necessity in vascular wound healing. Endothelial-specific knockout avoids developmental lethality and focuses on wound healing.
Point Mutation
Point mutations can dissect specific residues required for regulatory function, such as phosphorylation sites in signaling proteins. CRISPR knock-in of point mutants allows precise mechanistic interrogation.
Knock-in
Knock-in of reporters (e.g., fluorescent tags) or human disease variants into endogenous loci provides physiological expression and tracking. This is useful for studying microRNA targets or deubiquitinase localization.
Overexpression
CRISPR activation or transgenic overexpression of pro-angiogenic factors (e.g., VEGFA, miR-26a) can test sufficiency in accelerating wound healing. Overexpression models are valuable for therapeutic target validation.
How EDITGENE Supports regulation of vascular wound healing Research
Researchers studying regulation of vascular wound healing-related genes often need to determine whether a candidate gene is causally involved in endothelial or pericyte function. EDITGENE provides CRISPR-based services to generate precisely engineered cell and animal models for such mechanistic studies.
Contact EDITGENE today to design your custom CRISPR model for regulation of vascular wound healing research.
Frequently Asked Questions About regulation of vascular wound healing
What is GO:0061043?
GO:0061043 is the Gene Ontology term for regulation of vascular wound healing, defined as any process that modulates the rate, frequency, or extent of blood vessel formation from pre-existing vessels during restoration of damaged vasculature.
What genes are involved in regulation of vascular wound healing?
Key genes include MIR26A, OTUD1, GJA1 (connexin 43), ADRB2, VEGFA, and various chemokines such as CXCL12 and CCL2.
How is vascular wound healing regulated?
It is regulated by a balance of pro- and anti-angiogenic signals, including microRNAs, catecholamines, chemokines, reactive oxygen species, and pericyte-endothelial crosstalk.
What is the role of microRNA-26a in wound healing?
MicroRNA-26a regulates impaired angiogenesis in diabetic dermal wound healing, affecting endothelial function.
How does OTUD1 affect wound healing?
OTUD1 delays wound healing by regulating endothelial function and angiogenesis in diabetic mice.
What is the role of pericytes in vascular wound healing?
Pericytes regulate angiogenesis during cutaneous wound healing by providing stabilizing signals to endothelial cells.
How do catecholamines influence wound angiogenesis?
Catecholamines regulate angiogenesis in cutaneous wound healing, modulating endothelial cell behavior.
What is the connection between connexin 43 and wound healing?
Connexin 43 regulates endothelial cell pyroptosis through reactive oxygen species signaling, affecting wound healing.
Can CRISPR be used to study vascular wound healing?
Yes, CRISPR knockout, knock-in, and overexpression models enable causal testing of candidate genes in endothelial and pericyte populations.
What diseases are linked to dysregulated vascular wound healing?
Diabetic ulcers, chronic wounds, and cancer progression are linked to dysregulation of this process.
Conclusion
GO:0061043 regulation of vascular wound healing is a critical biological process that integrates angiogenic, inflammatory, and stabilizing signals to restore damaged vasculature. Its dysregulation contributes to diabetic wound healing impairment and cancer progression. Continued research using CRISPR models and molecular profiling will identify new therapeutic targets to modulate this process for clinical benefit.
References
- 1. Eming SA et al.. 2014. Wound repair and regeneration: mechanisms, signaling, and translation.. Sci Transl Med 6(265):265sr6 PMID: 25473038
- 2. Ishii T et al.. 2025. Pericyte-mediated regulation of angiogenesis during cutaneous wound healing in adult zebrafish.. Commun Biol 8(1):1101 PMID: 40715583
- 3. Chakroborty D et al.. 2020. Catecholamines in the regulation of angiogenesis in cutaneous wound healing.. FASEB J 34(11):14093-14102 PMID: 32949437
- 4. Zhang J et al.. 2026. OTUD1 delays wound healing by regulating endothelial function and angiogenesis in diabetic mice.. J Adv Res 80:1063-1081 PMID: 40300668
- 5. Ridiandries A et al.. 2018. The Role of Chemokines in Wound Healing.. Int J Mol Sci 19(10) PMID: 30340330
- 6. Icli B et al.. 2016. Regulation of impaired angiogenesis in diabetic dermal wound healing by microRNA-26a.. J Mol Cell Cardiol 91:151-9 PMID: 26776318
- 7. Jordan AM et al.. 2026. Angiocrine and pericrine signaling: how endothelial cells and pericytes drive cancer progression and therapy resistance.. Physiol Rev 106(1):87-119 PMID: 40952787
- 8. Zhang K et al.. 2022. Bioglass promotes wound healing by inhibiting endothelial cell pyroptosis through regulation of the connexin 43/reactive oxygen species (ROS) signaling pathway.. Lab Invest 102(1):90-101 PMID: 34521991
