Early plasma changes of HIF-1 alpha, matrix metalloproteinases-2 and - 9, and tissue inhibitor of matrix metalloproteinase-1 in patients with infantile hemangiomas treated with propranolol

普萘洛尔治疗婴幼儿血管瘤患者血浆中HIF-1α、基质金属蛋白酶-2和-9以及基质金属蛋白酶组织抑制剂-1的早期变化

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Abstract

BACKGROUND: Infantile hemangiomas (IH) are the most prevalent benign vascular tumors diagnosed in the pediatric population. Propranolol, a nonselective beta-adrenergic receptor antagonist, is the first-line treatment for IH. In this study, we aimed to assess the changes in plasma levels of HIF-1α, MMP-2, MMP-9, and TIMP-1 in patients with IH before and after one month of propranolol treatment. METHODS: Twenty children with IH and sixteen control subjects, admitted to the Department of Pediatric Surgery and Urology for elective inguinal hernia surgery, were included in this study. Blood plasma samples were obtained twice from the IH group (before and one month after initiating propranolol treatment) and once from the healthy control group. RESULTS: Patients treated with propranolol exhibited higher levels of MMP-2 both before (p = 0.0008) and after (p = 0.0006) treatment compared to the control group. The control group had higher levels of MMP-9 than the study group before propranolol treatment (p = 0.0267), but MMP-9 levels increased significantly after propranolol treatment in the study group (p = 0.0281). Plasma levels of TIMP-1 were considerably higher in the study group both before (p = 0.0097) and after (p = 0.0013) propranolol treatment compared to the control group. Additionally, HIF-1α levels were higher in the study group and showed an upward trend following propranolol treatment compared to the control group (p = 0.0114). CONCLUSIONS: This study provides insight into the plasma levels of MMP-2, MMP-9, TIMP-1, and HIF-1α involved in the involution of infantile hemangiomas during the early stage of propranolol treatment.

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