Increased shedding of microvesicles from intimal smooth muscle cells in athero-prone areas of the human aorta : implications for understanding of the predisease stage

Yuri V. Bobryshev, Murray C. Killingsworth, Alexander N. Orekhov

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)24-31
Number of pages8
JournalPathobiology
Volume80
Issue number1
DOIs
Publication statusPublished - 2012

Keywords

  • aorta
  • atherosclerosis
  • cell membranes

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