Bobryshev YV, Killingsworth MC, Orekhov AN.
Pathobiology. 2013;80(1):24-31. doi: 10.1159/000339430. Epub 2012 Jul 24
OBJECTIVE: This study evaluated whether a change in the content of matrix microvesicles might occur at the preatherosclerotic stage.
METHODS: Applying quantitative electron microscopic and immunohistochemical analyses, two areas of grossly normal segments of the thoracic aorta were compared: atherosclerosis-prone (AP) areas, situated at the dorsal aspect of the aorta along the rows of intercostal branch origins, and atherosclerosis-resistant (AR) areas, situated at the corresponding sites of the ventral aspect of the aorta.
RESULTS: The electron microscopic analysis showed that there were 1.4 times more microvesicles in AP areas than AR areas (p = 0.019). It was found that matrix microvesicles originated as a result of blebbing and shedding of surface membranes of smooth muscle cells. A quantitative analysis of the expression of ADP-ribosylation factor 6 (ARF6), which is known to be involved in membrane trafficking and microvesicle formation, showed that ARF6 expression was 1.3 times higher in AP areas than that in AR areas (p = 0.006). There was a positive correlation between the content of matrix microparticles and the expression of ARF6 by intimal smooth muscle cells (r = 0.61; p < 0.0001).
CONCLUSION: The present study supports the concept that alterations of the arterial intima occur at the predisease stage.