Microvascularization of the Vocal Folds: Molecular Architecture, Functional Insights, and Personalized Research Perspectives
Abstract
1. Background
Purpose of the Study: The Importance and Complexity of Vascularization in the Vocal Apparatus
2. Materials and Methods
3. Results
3.1. Personalized Approach on Embryonic Blood Vessel Formation: From Vasculogenesis to Angiogenesis
3.2. Normal Microvascular Structure of the Vocal Folds
3.3. The Microarchitecture of Blood Vessels Within the Mucosa of the Vocal Fold
3.4. Functional Role of the Vascular Network in the Human Vocal Fold Mucosa
3.5. Functional Importance of Capillary Pericytes in the Human Vocal Fold Mucosa
3.6. Key Mechanisms in Blood Vessel Formation: Endothelial Cell–Pericyte Interactions and Vascular Morphogenesis
3.7. The Role of Neuropeptides in the Regulation of Laryngeal Vascularization
- Neuropeptide Y (NPY): A 36-amino-acid peptide originally isolated from the porcine brain, with its molecular structure first elucidated by Tatemoto in 1982 [117]. NPY is co-localized with noradrenaline in sympathetic nerve terminals and is co-released with it. It is believed to play a significant role in angiogenesis during tissue development and repair processes [118,119].
- Vasoactive Intestinal Peptide (VIP): A 28-amino-acid peptide initially identified in porcine intestine in 1974. VIP is widely distributed in both the central and peripheral nervous systems and functions primarily in the relaxation of intestinal smooth muscles, dilation of peripheral blood vessels, and stimulation of salivary secretion [120].
- Calcitonin Gene-Related Peptide (CGRP): A 37-amino-acid peptide derived from alternative splicing of the calcitonin gene, first characterized in the 1980s. CGRP is extensively distributed throughout the central and peripheral nervous systems, where it plays key roles in vasodilation, pain transmission, and inflammatory processes [121].
4. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Marker | Associated Cell Types | References |
---|---|---|
PDGFR-β | Myofibroblasts, neurons and progenitors, mesenchymal cells, mesenchymal stem cells | [54,55,56,57] |
PDGFR-α | Mesenchymal cells, neural stem cells/B cells | [58,59,60,61] |
NG2 | vSMC, adipocytes, neuronal progenitors, glial cells, developing bone, muscle, skin | [62,63,64,65,66,67] |
Desmin | Skeletal muscle cells, cardiac smooth muscle cells, mesangial cells | [55,68,69,70] |
α-SMA | vSMC, myofibroblasts | [71,72,73,74] |
RGS5 | vSMC | [75,76,77] |
Endosialin | Myofibroblasts, fibroblasts, vSMC | [78,79,80] |
CD73 | Mesenchymal stem cells | [55] |
CD13 | vSMC, epithelial cells in the kidneys, tumor endothelial cells | [81,82,83] |
CD146 | Mesenchymal stem cells | [84] |
CD105 | Mesenchymal stem cells, endothelial cells, hematopoietic stem cells | [84,85,86,87] |
CD44 | Mesenchymal stem cells, lymphocytes, hematopoietic stem cells | [88,89] |
ANGPT1 | Hematopoietic progenitor cells, glioblastoma tumor cells, mast cells | [31,90] |
VEGF-A | Tumor cells, macrophages | [91,92] |
Functional Property | Endothelial Cells (ECs) | Pericytes |
---|---|---|
Tube Formation in 3D Collagen/Fibrin Matrices | ECs have the ability to form tubes in 3D collagen or fibrin matrices. | Pericytes do not form tubes in 3D matrices but invade as single cells. |
Vascular Guidance Tunnel Creation | ECs create vascular guidance tunnels during tubulogenesis in 3D matrices, aided by ECM proteolysis, particularly through MT1-MMP activity. | Pericytes invade in response to ECs in a manner dependent on PDGF-BB; recruitment results in more elongated and narrow EC tubes. |
Migration and Tube Assembly | ECs dramatically migrate within 3D matrices and co-assemble into tubes within vascular guidance tunnels. | Pericytes express very high levels of PDGFRβ and use this receptor to invade EC tubes and migrate along the tube abluminal surface. |
Proliferation during Tube Formation | ECs exhibit minimal to no proliferation during tube formation in 3D matrices. | Pericytes proliferate in response to ECs in a manner dependent on PDGF-BB and HB-EGF in 3D matrices. |
Co-assembly with Pericytes and Basement Membrane Formation | ECs co-assemble with pericytes to form capillary vessels and generate the vascular basement membrane. | Pericytes migrate along the EC tube abluminal surface within vascular guidance tunnels to facilitate basement membrane formation. |
Response to Hematopoietic Cytokines | Human ECs form tubes and sprout in response to stem cell cytokines (SCF, IL-3, SDF-1α) and FGF-2 under serum-free, defined conditions. | Human EC–pericyte tube co-assembly with accompanying basement membrane formation occurs in 3D matrices in response to hematopoietic cytokines. |
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Popa, R.-A.; Popa, C.-G.; Hînganu, D.; Hînganu, M.V. Microvascularization of the Vocal Folds: Molecular Architecture, Functional Insights, and Personalized Research Perspectives. J. Pers. Med. 2025, 15, 293. https://doi.org/10.3390/jpm15070293
Popa R-A, Popa C-G, Hînganu D, Hînganu MV. Microvascularization of the Vocal Folds: Molecular Architecture, Functional Insights, and Personalized Research Perspectives. Journal of Personalized Medicine. 2025; 15(7):293. https://doi.org/10.3390/jpm15070293
Chicago/Turabian StylePopa, Roxana-Andreea, Cosmin-Gabriel Popa, Delia Hînganu, and Marius Valeriu Hînganu. 2025. "Microvascularization of the Vocal Folds: Molecular Architecture, Functional Insights, and Personalized Research Perspectives" Journal of Personalized Medicine 15, no. 7: 293. https://doi.org/10.3390/jpm15070293
APA StylePopa, R.-A., Popa, C.-G., Hînganu, D., & Hînganu, M. V. (2025). Microvascularization of the Vocal Folds: Molecular Architecture, Functional Insights, and Personalized Research Perspectives. Journal of Personalized Medicine, 15(7), 293. https://doi.org/10.3390/jpm15070293