Peroxisome Proliferator-Activated Receptor Alpha (PPAR-α) as a Regulator of the Angiogenic Profile of Endometriotic Lesions.

Vasilios Pergialiotis,Zacharias Fasoulakis,George Daskalakis,Maximos Frountzas,Mairi Chrisochoidi,Konstantinos Kontzoglou,Despoina N Perrea

doi:10.7759/cureus.22616

Abstract

Endometriosis is a disease that affects a significant proportion of women and its infiltrative pattern is entirely dependent on the vascular supply of lesions. Several factors seem to trigger the process of angiogenesis in endometriotic lesions. During the last years, peroxisome proliferator-activated receptors (PPARs), a group of nuclear proteins that regulate gene transcription and that seem to regulate energy consumption and expenditure, have been also implicated in the pathophysiology of angiogenesis. Their ability to regulate the course of cancer and improve the survival rates of patients has been extensively studied and seems to be partially dependent on alteration of the vascular supply of malignant lesions. Research in the field of endometriosis is scarce in the international literature and mainly focused on PPAR-gamma. However, indirect evidence suggests that PPAR-alpha (PPAR-α) may also regulate the vascular supply of endometriotic lesions as well. Specifically, PPAR-α agonists seem to downregulate angiogenesis by increasing the expression of several anti-angiogenic molecules, including thrombospondin-1 (TSP-1) and gypenoside 140 (gp140), as well as factors that are involved in the mitogen-activated protein kinase cascade. In the present article, we summarize existing indirect and direct evidence that indicates the existence of an association between the expression of PPAR-α and endometriosis to help future research in this field.

Highlights

BackgroundEndometriosis is a disease that affects a significant proportion of women with a cumulative prevalence that reaches approximately 6.0% by the age of 40-44 years [1,2]
Several angiogenic factors have been proposed as diagnostic biomarkers that would help detect endometriosis including vascular endothelial growth factor (VEGF), nerve growth factor (NGF), fibroblast growth factor 2 (FGF-2), leptin, insulin-like growth factor-binding protein 3 (IGFBP-3), glycodelin, macrophage colony-stimulating factor (M-CSF), angiopoietin-1 and angiopoietin-2, microvessel density (MVD), endoglin, and thrombospondin-1 [7,8]
We describe the potential pathophysiological contribution of peroxisome proliferator-activated receptors (PPARs)-α in the pathophysiology of endometriosis, as we believe that these receptors may regulate the angiogenic profile of endometriotic lesions

Summary

Introduction

Endometriosis is a disease that affects a significant proportion of women with a cumulative prevalence that reaches approximately 6.0% by the age of 40-44 years [1,2]. Thrombospondins function as regulators of angiogenesis and seem to act as matricellular proteins as they interact with cell-surface receptors and several other molecules including proteases and growth factors This process results in the apoptosis of endothelial cells through activation of CD36 [22]. This effect seems to be triggered by an increase in angiogenesis that is manifested by an increased expression of PPAR-α in vascular endothelial cells as well as endometrial glandular and tumor cells To date, it remains unknown if the expression of the PPAR-α protein is the cornerstone of this regulatory mechanism or if this relies on the abundance of PPAR-α receptors. The authors reported that following pathology analysis of both the eutopic and ectopic endometrium, aberrant expression was observed, which indirectly supports the hypothesis of the potential effect of PPAR agonists in these patients

Conclusions

Disclosures

Findings

15. Erol A