Endothelial dysfunction may promote keloid growth

Abstract

Keloid is a cutaneous fibroproliferative disorder. It results from impaired wound healing that generates persistent inflammation and extensive deposition of collagen fibers in the wound/scar. Keloids tend to be worse in hypertensive patients. The present prospective cross-sectional study assessed whether endothelial dysfunction, which occurs in hypertension, associates with keloid formation and progression. This study included randomly selected patients with keloids who were assessed for surgical keloid treatment in 2013-2014. A series of nonkeloid patients admitted to the hospital was also recruited during this period. To measure endothelial function, all patients underwent digital reactive hyperemia peripheral arterial tonometry. Test results were expressed as reactive hyperemia index (RHI) and augmentation index (AI). In total, 57 patients with keloids and 19 nonkeloid controls were recruited. Keloid patients did not differ from the controls in terms of demographic or clinical variables, but had significantly worse RHI and AI values. Moreover, poor RHI and AI values associated with keloid development on binomial logistic regression. The keloid patients were then divided into four groups depending on whether their keloids started at age 0-12, 13-18, 19-29, or ≥30 years. Patients whose keloids arose before and well after puberty tended to have lower RHI than the controls, but these differences did not achieve statistical significance. However, these two groups did have significantly poorer AI values than the controls. Thus, endothelial dysfunction could cause keloid formation and/or aggravation. This indicates that vascular endothelial cells are important for wound healing.

Acne keloidalis nuchae and hypertension in black subjects: a case–control study

“…There is an interaction between these factors that may be mediated by an alteration in the ratio of metalloproteinase-1 matrix to tissue inhibitor of metalloproteinase-1 (MMP-1/TIMP-1) that promotes the deposition of extracellular matrix. Endothelial dysfunction, which also occurs in high blood pressure, may also be involved in the pathogenesis of keloid disorders [13]. In addition, activation of the renin-angiotensin system is known to cause angiotensin II-induced arterial vasoconstriction resulting in elevated blood pressure.…”

The Vascular Involvement in Soft Tissue Fibrosis—Lessons Learned from Pathological Scarring

“…Endothelial dysfunction is a hallmark of skin fibrotic conditions such as pathological cutaneous scars and cystic fibrosis. For example, our logistic regression analysis showed that patients with keloids were significantly more likely than the non-keloid controls to have poor reactive hyperemia index and augmentation index values: both indices are measures of endothelial function [11]. In fact, endothelial dysfunction plays such an important role in pathological scar development and progression that these cutaneous scars can be classified as primary and secondary pathological scars depending on whether the associated endothelial dysfunction is due to congenital abnormalities (e.g., mutations) or to externally-generated systemic (e.g., hypertension) or local (e.g., the tension on the scar) conditions [4].…”

The Role of the Renin-Angiotensin System and Vitamin D in Keloid Disorder—A Review

“…Improvement of KLs in hypertensive patients has been observed following treatment with anti-hypertensive medications, such as ACE inhibitors (66) and calcium channel blockers (69). Endothelial dysfunction, which also occurs in hypertension, may also participate in the pathogenesis of KD (1,70), and is associated with lung (71), liver (72), cardiac (73), and kidney (74) fibrosis.…”