Hemodynamics and Vascular Histology of Keloid Tissues and Anatomy of Nearby Blood Vessels

Abstract

Background: Keloids are red‚ invasive scars that are driven by chronic inflammation in the reticular dermis. The role of blood vessels in keloid behavior remains poorly understood. In the present study with 32 keloid patients, we examined the hemodynamics of keloid tissue, the anatomy of the blood vessels feeding and draining the keloids, and the vascular histology of keloids. Methods: Ten patients with large anterior chest keloids underwent near-infrared spectroscopy, which measured regional saturation of oxygen and total hemoglobin index in the keloid and surrounding skin. Another 10 patients with large chest keloids and three healthy volunteers underwent multidetector-low computed tomography. The extirpated chest keloids of 12 patients were subjected to histology with optical, CD31 immunohistochemical, and electron microscopy. Results: All keloids had a low regional saturation of oxygen and a high total hemoglobin index, which is indicative of blood congestion. Multidetector-low computed tomography revealed dilation of the arteries and veins that were respectively feeding and draining the keloid leading edge. Hematoxylin-eosin staining and CD31 immunohistochemisty revealed considerable neovascularization in the keloid leading edge but not in the center. Electron microscopy showed that the lumens of many vessels in the keloid center appeared to be occluded or narrowed. Conclusions: Keloids seem to be congested because of increased neovascularization and arterial inflow at the leading edge and blocked outflow due to vascular destruction in the center. The surrounding veins seem to expand in response to this congested state. Methods that improve the blood circulation in keloids may be effective therapies.

CD74+fibroblasts proliferate upon mechanical stretching to promote angiogenesis in keloid

“…Initially, using CD31 as a marker for vasculature, we compared the vasculature area between the leading edge and the center of keloids. The average vasculature area was found to be 10% in the leading edge and 3% in the keloid center, confirming the previously reported (53) higher vasculature density at the leading edge of keloids compared to the center (Figure 3B). Subsequently, employing PDGFRA as a pan-fibroblast marker (18), we compared the proportion of CD74 + fibroblasts, identified as cells double-positive for PDGFRA and CD74 staining, between the leading edge and the center of keloids.…”

“…The fibro-proliferative and invasive nature of keloids necessitates a robust angiogenic mechanism at its command to transport oxygen and nutrients. Indeed, enhanced neo-vascularization activities of endothelial cells (53) as well as fibroblasts with stronger pro-angiogenic secretory phenotypes (33) were observed at the leading edge of keloids compared to keloid centers. The standard-of-care treatment modalities for keloids, including surgical excision, compression dressings, laser therapy, radiation, corticosteroids, and cytotoxic drugs, offer only limited efficacy with a high risk of recurrence (63).…”

The Association of Keloid Site with its Histopathological Features: an Analytical Observational Study

“…14 This study suggests a significant relationship between the site of keloid and dermal vascularization, whereas vascularization was more common at the edge of the lesion, as this site has more robust neovascularization compared to the center of the keloid lesion, which tends to have fewer vessels, leading to ischemia. 13,19 Most of our study subjects had keloids on their ears and chests with vascularization features on histopathological examination. Another study by Matsumoto revealed that there is an increase in vascularization surrounded by collagen hyalinization in the papillary dermis of ear keloids.…”

“…12 The formation of neovascularization, along with an increase in inflammatory cells, is the effect of mechanical stimulation on body areas with high tension. 13 Ogawa hypothesized that keloids result from an exaggerated inflammatory response by a strong mechanical stimulus in high-tension areas. 14 Histopathological features of keloids include thickened epidermis as well as vascularization and infiltration of inflammatory cells in dermis.…”

Characterization of the skin keloid microenvironment

“…Keloids are characterized by the excessive deposition of collagen during abnormal wound healing [ 1 ], which leads to a fibroproliferative inflammatory response with neovascularization at the leading edge [ 2 ]. Life quality of keloid patients is dramatically affected by physical symptoms, including pruritus and pain, as well as psychological barriers [ 3 ].…”