Hypoxia-Inducible Factor-1α (HIF-1α) as a Biomarker for Changes in Microcirculation in Individuals with Systemic Sclerosis.

Abstract

Systemic sclerosis is an autoimmune disease characterized by tissue fibrosis and microangiopathy. Vascular changes such as a decrease in capillary density diminish blood flow and impair tissue oxygenation. Reliable ways to monitor disease activity and predict disease progression are desired in the process of patient selection for clinical trials and to optimize individual patient outcomes. Hypoxia-inducible factor-1 (HIF-1) is a dimeric protein complex that plays an integral role in the body's response to hypoxia. Our study aimed to investigate the potential abnormalities of HIF-1α plasma concentration and its possible association with disease activity and vascular abnormalities in patients with systemic sclerosis. Blood plasma levels of HIF-1α were measured in patients with systemic sclerosis (n = 50) and in healthy individuals (n = 30) using commercially available ELISA test kits. The results showed a marked increase in HIF-1α levels in patients with systemic sclerosis (3.042ng/ml [2.295-7.749]) compared to the control group (1.969ng/ml [1.531-2.903] p < 0.01). Patients with diffuse cutaneous SSc (2.803ng/ml, IQR 2.221-8.799) and limited cutaneous SSc (3.231ng/ml, IQR 2.566-5.502) exhibited elevated serum HIF-1α levels compared to the control group (p < 0.01). We found a notable increase in HIF-1α plasma concentration in patients with an "active" pattern (6.625ng/ml, IQR 2.488-11.480) compared to those with either an "early" pattern (2.739, IQR 2.165-3.282, p < 0.05) or a "late" pattern (2.983ng/ml, IQR 2.229-3.386, p < 0.05). Patients with no history of digital ulcers had significantly higher levels of HIF-1α (4.367ng/ml, IQR 2.488-9.462) compared to patients with either active digital ulcers (2.832ng/ml, IQR 2.630-3.094, p < 0.05) or healed digital ulcers (2.668ng/ml, IQR 2.074-2.983, p < 0.05). Our results indicate that HIF-1α may serve as a biomarker in assessing microcirculatory changes in individuals with systemic sclerosis.