The endothelium, the major regulator of vascular homeostasis, plays an essential role in the regulation of vascular tone, cellular adhesion, thromboresistance,
Dinaciclib cell proliferation, and vessel wall inflammation. Endothelial dysfunction is an early marker for atherosclerosis, preceding angiographic or ultrasonic evidence of atherosclerotic plaques [28] and [29]. It is well established that an elevated level of Ox-LDL, the main atherogenic class of lipoprotein, is one of the most important risk factors for atherosclerosis and cardiovascular morbidity [30]. Serum homocysteine (Hcy), on the other hand, is considered as a clinical risk factor for coronary artery disease, as well as other arterial and venous occlusive diseases [31]. In the present study, we have provided the first evidence that HSP70 is trafficked via a non-classical exosomal pathway in arterial endothelial cells. Hcy and Ox-LDL significantly enhance the exosome-dependent HSP70 release from arterial endothelial cells. Moreover, we have demonstrated that extracellular HSP70 activates monocytes but not endothelial cells. These results suggest that the exosome-dependent release of HSP70 from endothelial
cells provides a novel paracrine mechanism to regulate vascular homeostasis.
