title: ACE2 and AT4R are present in diseased human blood vessels.
abstract: A growing body of evidence suggests that the angiotensin II fragments, Ang(1-7) and Ang(3-8), have a vasoactive role, however ACE2, the enzyme that produces Ang(1-7), or AT4R, the receptor that binds Ang (3-8), have yet been simultaneously localised in both normal and diseased human conduit blood vessels. We sought to determine the immunohistochemical distribution of ACE2 and the AT4R in human internal mammary and radial arteries from patients undergoing coronary artery bypass surgery. We found that ACE2 positive cells were abundant in both normal and diseased vessels, being present in neo-intima and in media. ACE2 positive immunoreactivity was not present in the endothelial layer of the conduit vessels, but was clearly evident in small newly formed angiogenic vessels as well as the vaso vasorum. Endothelial AT4R immunoreactivity were rarely observed in either normal and diseased arteries, but AT4R positive cells were observed adjacent to the internal elastic lamine in the internal mammary artery, in the neo-intima of radial arteries, as well as in the media of both internal mammary artery and radial artery. AT4R was abundant in vaso vasorum and within small angiogenic vessels. Both AT4R and ACE2 co-localised with smooth muscle cell alpha actin. This study identifies smooth muscle cell alpha actin positive ACE2 and AT4R in human blood vessels as well as in angiogenic vessels, indicating a possible role for these enzymes in pathological disease.
authors.affiliation: Department of Cardiology, Austin Health, Heidelberg 3084, Australia. azulli@unimelb.edu.au
authors.forename: A
authors.initials: A
authors.lastname: Zulli
authors.forename: L M
authors.initials: LM
authors.lastname: Burrell
authors.forename: B F
authors.initials: BF
authors.lastname: Buxton
authors.forename: D L
authors.initials: DL
authors.lastname: Hare
mesh_terms: D000199:Actins / Q000032:analysis; D000085962:Angiotensin-Converting Enzyme 2; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000201:enzymology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000737:chemistry* / Q000201:enzymology; D006801:Humans; D008323:Mammary Arteries / Q000737:chemistry* / Q000166:cytology / Q000201:enzymology; D009131:Muscle, Smooth, Vascular / Q000737:chemistry* / Q000201:enzymology; D032389:Myocytes, Smooth Muscle / Q000737:chemistry / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000032:analysis*; D017534:Radial Artery / Q000737:chemistry* / Q000166:cytology / Q000201:enzymology; D011945:Receptors, Angiotensin / Q000032:analysis*
chemical_list: C090830:AT4 receptor; D000199:Actins; D011945:Receptors, Angiotensin; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2