Objectives: Heregulins (HRGs) are known to induce expression of angiogenic factors such as cysteine rich-61 (CYR61) and collectively to promote neoangiogenesis. Along with extracellular matrix remodelling, mediated by matrix metalloproteinases (MMPs), these factors are important in atherogenesis. The aim of the present study was to investigate HRG, CYR61 and MMP-9 expression and their relationship with clinical and histopathological findings in carotid occlusive disease.
Materials and methods: Specimens of human carotid atherosclerotic plaque (n=90) were obtained by endarterectomy. Expression of HRG, CYR61 and MMP-9 was assessed by immunohistochemical and Western blot analysis. Associations between protein expression and degree of carotid stenosis, presence of symptoms, presence of an infarct in CT scan and carotid plaque histopathology were investigated.
Results: An increase in HRG, CYR61 and MMP-9 expression was found, particularly in neovascularized regions of the plaques. High HRG expression was associated with the degree of carotid stenosis (p=0.028) and plaque histopathology (p=0.002). More than half of specimens from plaques with >90% stenosis had intense expression of CYR61 (p=0.047). Increased expression of MMP-9 was associated with degree of stenosis and presence of cerebral infarct on CT scan (p=0.05).
Conclusion: HRG, CYR61 and MMP-9 are highly expressed in human atherosclerotic carotid plaques. The association with the degree of stenosis and/or plaque histopathology implies an involvement in lesion progression.