Transition from atherosclerosis to aortic aneurysm in humans coincides with an increased expression of RAS components.
While the renin-angiotensin system (RAS) is widely recognized to be involved in atherosclerosis, its potential role in the progression from atherosclerotic lesions to abdominal aortic aneurysm (AAA) is poorly understood. The present study aimed to investigate which components of the RAS may render the atherosclerotic aorta aneurysmatic. The expression of renin, prorenin/renin receptor, angiotensinogen, AT1- and AT2 receptors, cathepsin D, cathepsin G and chymase was examined by immunoblotting and immunohistochemistry in human atherosclerotic, aneurysmatic and healthy aortic tissues obtained from patients undergoing elective repair or at autopsy. AT1- and AT2 receptor mRNA expression was determined using quantitative real-time RT-PCR. All investigated local RAS components were up-regulated in atherosclerotic as compared to healthy tissues. AAA compared to atherosclerosis was characterized by a further increase in the expression of all RAS components except for the AT2 receptor. Cathepsin D was exclusively up-regulated in AAA. Most RAS components co-localized with infiltrating leukocytes or mast cells pointing to their contribution to inflammatory processes. Due to their proteolytic features, some RAS components (cathepsin D and cathepsin G and chymase) may contribute to AAA formation by accessory mechanisms. Taken together, our data suggest that in humans, RAS activation is not just a key-player in the pathogenesis of atherosclerosis, but that a further increasing activation may be involved in the transition from atherosclerosis to AAA.
Kaschina
Elena
E
Center for Cardiovascular Research/Institute of Pharmacology, Charité-Universitätsmedizin Berlin, Germany. elena.kaschina@charite.de
Scholz
Hans
H
Steckelings
U Muscha
UM
Sommerfeld
Manuela
M
Kemnitz
Ulrich Rudolf
UR
Artuc
Metin
M
Schmidt
Sven
S
Unger
Thomas
T
D000368:Aged; D000369:Aged, 80 and over; D000783:Aneurysm / Q000473:pathology; D001014:Aortic Aneurysm / Q000175:diagnosis* / Q000473:pathology; D050197:Atherosclerosis / Q000175:diagnosis* / Q000473:pathology; D002402:Cathepsin D / Q000096:biosynthesis; D018450:Disease Progression; D005260:Female; D006801:Humans; D007249:Inflammation; D007962:Leukocytes / Q000166:cytology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D012084:Renin-Angiotensin System; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D002402:Cathepsin D