Concentration polarization of ox-LDL activates autophagy and apoptosis via regulating LOX-1 expression.

Here we demonstrate that "concentration polarization" of ox-LDL enhances LOX-1 expression and ox-LDL uptake. It damages cell surface heparan sulfate proteoglycans (HSPG) and activates LOX-1 dependent autophagy and apoptosis. We also show that ox-LDL concentration polarization occurs on the surface of rabbit thoracic aorta and induces autophagy and apoptosis. In order to investigate the significance of swirling flow on LOX-1 expression, HSPG damage, autophagy and apoptosis in the arterial system, an ex vivo model of swirling flow was developed. We observed that swirling flow decreases relative wall concentration of ox-LDL, inhibits LOX-1 expression, protects HSPG from damage, and decreases both autophagy and apoptosis. Taken together, our data suggest that ox-LDL concentration polarization plays an important role in the localization of atherosclerotic lesions concomitant with LOX-1 dependent autophagy and apoptosis. These observations also suggest a novel mechanism by which swirling flow in the arterial system protects arterial wall from atherogenesis.