O36	A new ACE on the table: ACE2 expression in human atherosclerosis.
1J.C.Sluimer, 2I.Hamming, 3J.M.Gasc, 2H.Van Goor, 4L.H.Van den Akker, 3P.Corvol, 1M.J.Daemen, 1A.P.Bijnens
1Department of Pathology, CARIM, University of Maastricht, Maastricht, NL; 2Department of Pathology, University Medical Center Groningen, Groningen, NL; 3Collège-de-France, INSERM U36, Paris, FR; 4Department of Surgery, Maasland Hospital, Sittard, NL.

Angiotensin Converting Enzym (ACE) 2 is a recently identified homologue of ACE and the receptor for SARS coronavirus. It is highly expressed in human heart and kidney and thought to influence cardiac function and blood pressure. ACE2 inactivates angiotensin (Ang) II, a vasoconstrictive, pro-inflammatory and pro-fibrotic agent. As Ang II has well described pro-atherogenic effects, we hypothesize that ACE2 might play a role in atherogenesis. Therefore, we used in situ hybridization (n=6) and immunohistochemistry (n=33) to study the spatiotemporal expression pattern of ACE2 in human carotid arteries with early, stable advanced or thrombus-containing atherosclerotic lesions. In addition, the protein expression pattern was studied in non-diseased veins and mammary arteries. In situ hybridization demonstrated that RNA was expressed in the vascular media and intima, more specifically in shoulder regions of the lesion and lining the lumen. ACE2 mRNA was strongly expressed in smooth muscle cells (SMC), endothelial cells (EC) and macrophages of early, stable advanced and thrombus-containing carotid lesions. Immunohistochemistry allowed for the determination of a potential association of ACE2 expression with atherosclerotic load. In line with our observations of ACE2 mRNA expression, ACE2 immunoreactivity was strongly present in SMC and EC of the media and intima and modestly in intimal macrophage foam cells. EC and medial ACE2 immunoreactivity was similarly present in the non-diseased and atherosclerotic vessel wall and thus not associated with disease status. However, intimal ACE2 immunoreactivity was differential between atherosclerotic stages. In SMC it was most intense in stable advanced human lesions, whereas in macrophages it increased to a maximum in thrombus-containing lesions. In conclusion, ACE2 is expressed in human non-diseased and atherosclerotic blood vessels. The high ACE2 RNA and protein expression in intimal SMC and macrophages, which is associated with progression of atherosclerotic lesions, provides further evidence for a role of this novel molecule of the RAAS in the pathogenesis of atherosclerosis.

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