Plasma Angiotensin-converting Enzyme Levels in Patients With Keloids and/or Hypertension

Introduction. Keloidal scarring is associated with hypertension and its pathogenesis remains poorly understood. The role of angiotensin-converting enzyme (ACE) in both hypertensive and fibrotic conditions suggests ACE may be a common mechanism for the pathogenesis of both hypertension and keloids. Objective. This paper aims to investigate the possible underlying role of ACE in keloid pathogenesis. Materials and Methods. Plasma samples were collected from participants with and without keloids. Enzyme-linked immunosorbent assays were then performed to determine ACE levels in the plasma samples. The plasma ACE levels of patients with and without keloid scarring were compared, while controlling for hypertension. Results. The 78 samples (39 keloid participants, 39 controls) were divided into 4 cohorts of either 18 (hypertensive) or 21 (normotensive) participants. The mean ± standard deviation ACE levels were 77.9 ± 31.2 ng/mL for the hypertensive keloid group (n = 18), 69.2 ± 18.8 ng/mL for the normotensive keloid group (n = 21), 72.7 ± 21.5 ng/mL for the hypertensive control group (n = 18), and 77.6 ± 18.5 ng/mL for the normotensive control group (n = 21). No significant differences in the mean plasma ACE levels were found between any of the 4 groups. Conclusions. Although the data showed no significant correlation between plasma ACE levels, keloids, and hypertension, additional studies may be pursued to determine the possible underlying role of ACE in keloid pathogenesis.

Keloid scars are aberrant scars that grow beyond the confines of the original wound due to an exaggerated healing response. Keloid pathogenesis remains poorly understood, with no fully effective treatment currently available for patients. Keloid scarring is associated with other medical conditions; in particular, the association between keloids and hypertension has been considerably characterized.¹

One important enzyme involved in blood pressure regulation as well as adverse fibrous remodeling in multiple organ systems is angiotensin-converting enzyme (ACE). Compared with hypertrophic or normal scars, ACE levels are elevated in keloid scars.² The presence of ACE in both hypertensive and fibrotic conditions suggests that ACE and the renin angiotensin system (RAS) may be a common mechanism for the pathogenesis of both hypertension and keloids. Therefore, to investigate the possible underlying role of ACE in keloid pathogenesis, plasma ACE levels of patients with and without keloid scarring, while controlling for hypertension, were compared, with the hypothesis that plasma ACE levels would be elevated in keloid patients compared with nonkeloid patients.

Plasma samples were obtained from participants enrolled in the Genetic Causes of Keloid Formation Study, an Institutional Review Board-approved study at the University of Texas Southwestern Medical Center (Dallas, TX). Participants were recruited from patients seen in outpatient clinics from the Departments of Dermatology and Internal Medicine, as well as from the Dallas-Fort Worth community. All participants were at least 18 years of age; able to read, write, and/or speak English; and were able to give informed consent.

Keloid samples were collected from participants with the clinical and/or histologic diagnosis of keloids; control samples were obtained from participants of comparable age and gender with no personal or family history of keloids (Table). An equivalent number of normotensive or hypertensive individuals were collected into both groups. Only African American patients were included to prevent possible confounding results from genetic differences between racial groups. Patients who were prescribed ACE inhibitors or angiotensin receptor blockers were excluded from the study. Human ACE-linked immunosorbent assays were then performed in duplicate, following standard protocol, to determine ACE levels in the plasma samples. Results were analyzed using an unpaired t test via GraphPad QuickCalcs online software (GraphPad Software, La Jolla, CA) to compare means and standard deviations within the different cohorts.

The 78 samples (39 keloid participants, 39 controls) were divided into 4 cohorts of either 18 (hypertensive) or 21 (normotensive) participants. The mean ± standard deviation ACE levels were 77.9 ± 31.2 ng/mL for the hypertensive keloid group (n = 18), 69.2 ± 18.8 ng/mL for the normotensive keloid group (n = 21), 72.7 ± 21.5 ng/mL for the hypertensive control group (n = 18), and 77.6 ± 18.5 ng/mL for the normotensive control group (n = 21) (Table). No significant differences in the mean plasma ACE levels were found between any of the 4 groups. In addition, no significance was found after further subdividing patients within the keloid cohorts per the severity of their keloids.

The ACE is an extensively studied enzyme involved in both blood pressure regulation and fibrous remodeling. Studies have found a correlation between ACE and other conditions, including sarcoidosis and systemic scleroderma.^3,4 Other reports show an increase in cutaneous ACE activity in keloid scarring and the possible efficacy of ACE inhibitors for keloid treatment.^2,5

Possible limitations of this study include a relatively small study size and the analysis of only 1 racial group.

Although the data did not show a significant correlation between plasma ACE levels, keloids, and hypertension, additional studies may be pursued to determine what role(s) RAS plays in keloid pathogenesis.

The authors thank Helen Hobbs, MD; Jonathan Cohen, PhD; and Teresa Eversole from the McDermott Center for Human Growth and Development, UT Southwestern Medical Center; Shawna Nesbitt, MD, from the Department of Internal Medicine, UT Southwestern Medical Center; and Benjamin Chong, MD, MSCS, Irene Dougherty, and Rose Cannon from the Department of Dermatology, UT Southwestern Medical Center (Dallas, TX).

Affiliations: Department of Dermatology, UT Southwestern Medical Center, Dallas, TX; and McDermott Center for Human Growth and Development, UT Southwestern Medical Center

Correspondence: Donald A. Glass II, MD, PhD, Department of Dermatology, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9069; donald.glass@utsouthwestern.edu

Disclosure: This study was supported by the UT Southwestern Medical Student Summer Research Program, the Dermatology Foundation, the Dedman Family Scholar in Clinical Care Endowment, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award No. K23 AR069728.