Paracrine activity of heparin-binding EGF-like growth factor in atherogenesis: an immunohistochemical study

Cells involved in atherogenesis produce growth factors crucial for the progression of the atherosclerotic lesions. One of them is the heparin-binding EGF-like growth factor (HB-EGF), a member of the epidermal growth factor (EGF) family, synthesized as a transmembrane precursor (proHB-EGF). This anchored insoluble juxtacrine growth factor can be converted into a soluble molecule with paracrine activity and mature HB-EGF is released in the extracellular matrix from the cell surface. HB-EGF is a potent stimulator of cell proliferation, migration and cell motility and several studies show that HB-EGF is associated with pathologies of hyperplasia of smooth muscle cells including atherosclerosis.

We localized HB-EGF by immunohistochemistry within the atherosclerotic lesions collected from right or left internal carotid artery of 20 patients with evident clinical symptoms.

In the 20 samples we tested, the proportion of positive samples was significant. Considering the only positive samples the proportion difference related to the gender of patients was highly significant.

The aim of our investigation was to better understand if this growth factor exerts its role through a juxtacrine or paracrine mechanism, or both in the process of atherogenesis. According to the results, the paracrine role of HB-EGF was clear.