title: Co-localization of angiotensin-converting enzyme 2-, octomer-4- and CD34-positive cells in rabbit atherosclerotic plaques.
abstract: Angiotensin-converting enzyme 2 (ACE2) is a novel enzyme with possible implications in the treatment of blood pressure disorders. Recent evidence suggests that an upregulation of ACE2 can be stimulated by all-trans retinoic acid (at-RA); however, at-RA also affects regulation of the stem-cell marker octomer-4 (Oct-4) and thus cellular differentiation. We have previously shown that smooth muscle cells and macrophages present within rabbit atherosclerotic plaques are positive for ACE2, Oct-4 and the haematopoietic stem-cell marker CD34. Thus, to provide evidence that possible at-RA treatment could affect both plaque cellular biology (via effects on cellular differentiation) and blood pressure (via ACE2), it is vital to show that cells with atherosclerotic plaques co-express all three markers. Thus, we sought to provide evidence that a subset of cells within atherosclerotic plaques is positive for ACE2, Oct-4 and CD34. We used New Zealand White rabbits that were fed a control diet supplemented with 0.5% cholesterol plus 1% methionine for 4 weeks and then allowed to consume a normal diet for 10 weeks. Immunohistochemistry was performed by standard techniques. We report that ACE2, Oct-4 and CD34 were all present within atherosclerotic plaques. Although macrophages were positive for all three markers, spindle-shaped cells in the media did not show all three markers. The endothelium overlying normal arterial wall showed positive Oct-4 and ACE2 immunoreactivity, but CD34 immunoreactivity was patchy, indicating that such cells might not have fully differentiated. It is concluded that cells in atherosclerotic plaques express co-express ACE2, Oct-4 and CD34. Further studies aimed at establishing the effects of all-trans retinoic acid on blood pressure and atherosclerotic cell differentiation are warranted.
authors.affiliation: Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Melbourne, Victoria, Australia. azulli@unimelb.edu.au
authors.forename: Anthony
authors.initials: A
authors.lastname: Zulli
authors.forename: Sudarshan
authors.initials: S
authors.lastname: Rai
authors.forename: Brian F
authors.initials: BF
authors.lastname: Buxton
authors.forename: Louise M
authors.initials: LM
authors.lastname: Burrell
authors.forename: David L
authors.initials: DL
authors.lastname: Hare
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D001012:Aorta, Abdominal / Q000473:pathology; D050197:Atherosclerosis / Q000201:enzymology* / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006973:Hypertension / Q000201:enzymology / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011817:Rabbits
chemical_list: D018952:Antigens, CD34; D050814:Octamer Transcription Factor-3; D007703:Peptidyl-Dipeptidase A; D000085962:Angiotensin-Converting Enzyme 2