Microvascularization of the Vocal Folds: Molecular Architecture, Functional Insights, and Personalized Research Perspectives

Abstract

Introduction: The vascular architecture of the vocal folds plays a critical role in sustaining the dynamic demands of phonation. Disruptions in this microvascular system are linked to various pathological conditions, including Reinke's edema, hemorrhage, and laryngeal carcinoma. This review explores the structural and functional components of vocal fold microvascularization, with emphasis on pericytes, endothelial interactions, and neurovascular regulation. Materials and Methods: A systematic review of the literature was conducted using databases such as PubMed, Scopus, Web of Science, and Embase. Keywords included "pericytes", "Reinke's edema", and "vocal fold microvascularization". Selected studies were peer-reviewed and met criteria for methodological quality and relevance to laryngeal microvascular physiology and pathology. Results: The vocal fold vasculature is organized in a parallel, tree-like pattern with distinct arterioles, capillaries, and venules. Capillaries dominate the superficial lamina propria, while transitional vessels connect to deeper arterioles surrounded by smooth muscle. Pericytes, present from birth, form tight associations with endothelial cells and contribute to capillary stability, vessel remodeling, and mechanical protection during vibration. Their thick cytoplasmic processes suggest a unique adaptation to the biomechanical stress of phonation. Arteriovenous anastomoses regulate perfusion by shunting blood according to functional demand. Furthermore, neurovascular control is mediated by noradrenergic fibers and neuropeptides such as VIP and CGRP, modulating vascular tone and glandular secretion. The limited lymphatic presence in the vocal fold mucosa contributes to edema accumulation while also restricting carcinoma spread, offering both therapeutic challenges and advantages. Conclusions: A deeper understanding of vocal fold microvascularization enhances clinical approaches to voice disorders and laryngeal disease, offering new perspectives for targeted therapies and regenerative strategies.

Keywords: Reinke’s edema; capillary permeability; endothelial cells; microvascularization; pericytes; personalized vascular signaling; vocal folds.

Figure 1

PRISMA flow diagram illustrating the study selection process for the systematic review. Initially, 7171 records were identified through database searching, of which 5769 duplicates were removed. After screening titles and abstracts, 352 records were excluded for not meeting the eligibility criteria. A total of 181 full-text articles were assessed for eligibility, with 58 excluded due to methodological quality concerns, resulting in 123 studies included in the final analysis.

Figure 2

Vasculogenesis in embryos (left) refers to the formation of new blood vessels from primitive mesodermal cells. Signals from nearby endodermal cells stimulate these precursor cells to become angioblasts, which cluster to form blood islands. These islands then merge to create a primitive vascular network that later develops into the arteriovenous system. In contrast, angiogenesis (right) is the process of generating new blood vessels from existing ones. This begins with the breakdown of the extracellular matrix, the detachment of pericytes, and the emergence of tip cells. These tip endothelial cells, which do not divide, migrate toward sources of proangiogenic signals and are followed by proliferating stalk cells.