Increased PrPC expression correlates with endoglin (CD105) positive microvessels in advanced carotid lesions

Abstract

Normal cellular prion protein (PrP(C)) has multiple functions but its role in the development of atherosclerosis has not been studied. Our pilot microarray data showed increased expression of PrP(C) in tissue samples of complicated carotid lesions. Therefore in this study, we aimed to investigate its localisation within atherosclerotic arteries and its concentration in patient plasma. PrP(C) expression was examined using an enzyme immunometric assay (EIA) in plasma from patients undergoing endarterectomy. Carotid specimens and control vascular transplants were studied for PrP(C) and CD105 (endoglin, a marker of active vessels) expression by immunohistochemistry and real-time PCR. Patients with carotid disease had higher levels of plasma PrP(C) than the control group [4.35 ng/ml (n = 22; 3.1-5.3) vs. 1.95 ng/ml (n = 21; 1.1-2.5), P < 0.001]. Furthermore, CD105-positive plaques had higher PrP(C) expression which colocalized with CD105 in neovessels. There was a significant correlation between mRNA expression of PrP(C) and CD105 in tested plaques (P < 0.001; r = 0.7) supporting our immunohistochemical findings. We conclude that PrP(C) is expressed in carotid specimens and may be associated with neovessel growth or survival in these plaques. Our results suggest a role for PrP(C) in modulating neovessel formation in complicated plaques.

Circulating Endothelial Microparticles in Diabetes Mellitus

“…Of note, the use of CD31 as a sole marker for EMP detection is controversial and has not been consistently shown to distinguish EMPs from PMPs. CD105 (endoglin) is a transmembrane glycoprotein found in the vast majority of the microvessels in atheroma and with a pronounced expression around the periphery of the lipid core [29]. Vascular cell adhesion molecule-1 (VCAM-1, CD106) is expressed on activated endothelial cells and participates in the inflammatory initiation and progression of atherosclerotic plaques [30, 31].…”

Behind the Link between Copper and Angiogenesis: Established Mechanisms and an Overview on the Role of Vascular Copper Transport Systems

“…From a pathological point of view, the activation of the PrP C gene is increased in response to hypoxia that occurs during ischaemic events [119,203,204,205]. Furthermore, in vitro studies clearly indicate that PrP C plays a critical role in the vascular recovery of brain- and carotid-damaged regions [206,207]. …”

The Role of TGF-&beta; and TGF-&beta; Receptors in Atherosclerosis

“…Also other studies showed higher expression of endoglin in atherosclerotic vessels when compared with non-diseased vessels, suggesting that endoglin participates in atherogenesis (Piao and Tokunaga, 2006;Tashiro et al, 2002). Additionally, endoglin expression was linked to neo-angiogenesis within atherosclerotic aortic and carotid plaques, supporting its role in this process (Krupinski et al, 2008). Moreover, endoglin serum levels were found to be elevated in patients with atherosclerosis and correlated with total cholesterol levels (Blann et al, 1996).…”