Vascular Remodelling is Impaired in Parkinson Disease

Abstract

Objective: We have previously reported vascular degeneration of human Parkinson disease (PD). In which we described degenerative pathology of endothelial cells and its association with increased string vessels in the grey matter of middle frontal gyrus (MFG). Growth factors, for example platelet-derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF), involve in vascular remodelling by promoting cell proliferations and angiogenesis through capillary pericytes. Thus current study examined the hypothesis whether vascular degeneration in human PD is associated with impairment of vascular remodelling. Methods: Using tissue microarray method we conducted immuno histochemical staining in the grey matter of MFG of human PD (n=17) and age-matched control cases (n=17). The expression of PDGF receptor-beta, proliferating cell nuclear antigen and phosphorylation of IGF-1 receptor in capillaries, IGF binding protein-2 and VEGF were evaluated using automated image analysis software. Results: PDGF receptor-beta was specifically expressed in the pericytes which formed capillary morphology. Compared to the age-matched control cases, there were significant decrease in PDGF receptor-beta positive capillaries (p<0.05; p<0.01), proliferating vascular cells (p<0.05) and VEGF (p<0.05) in the PD cases. There no difference in phosphorylation of IGF-1 receptors, expressed in the capillaries between the groups. We found a significant increase in IGF binding protein-2, expressed in the astrocytes of PD when compared to the control cases (p<0.05). Interestingly the levels of phosphorylated IGF receptors in the capillaries were significantly correlated with the numbers of pericytes and proliferating cells in capillaries (p=0.001). Conclusion: Impaired PDGF function in the pericytes, reduced cell proliferation and VEGF suggested that the ability of vascular remodelling is impaired in PD. The maintained IGF-1 function appeared to be ineffective to retain vascular remodelling process in PD. The up-regulation of IGF binding protein-2 may suggest a role for autocrine/ paracrine of IGF-1 in PD.