Cathepsin G is associated with atheroma formation in human carotid artery.
OBJECTIVE
To elucidate the organization of the tissue angiotensin system, we investigated the expression and cellular localization of angiotensin system components and cathepsins D and G, potentially involved in intraparietal angiotensin II formation and atheroma.


METHODS
Total RNA was extracted from atheroma plaque, fatty streaks and macroscopically intact tissue obtained during carotid endarterectomy in 21 hypertensive patients. mRNA levels were compared between these tissues using a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). In situ hybridization and immunohistochemistry were used to define the cellular localization of the transcripts and their respective proteins.


RESULTS
Apart from renin and angiotensin type 2 (AT2) receptors, which were never detected, the studied mRNAs could be measured in all patients. Angiotensin-converting enzyme (ACE) mRNA was increased five-fold in atheroma, and angiotensin type 1 receptor (AT1) mRNA decreased 2.5-fold in atheroma and 1.4-fold in fatty streaks compared to intact tissue. A two-fold increase in cathepsin G mRNA was observed in atheroma plaque. In atheroma and intact tissue, significant positive correlations were found between cathepsin G and angiotensinogen, AT1 receptor and ACE mRNAs. Angiotensinogen and cathepsin mRNAs and proteins were detected in both arterial layers. AT1 immunoreactivity was mainly associated with alpha-actin-positive cells.


CONCLUSIONS
All components required for angiotensin II formation are expressed locally in the arterial wall, where, in the absence of renin, cathepsin G could be a major angiotensin-generating enzyme. Overexpression of ACE and cathepsin G may lead to angiotensin II overproduction and contribute, with decreased number of differentiated smooth muscle cells, to the lower amount of AT1 receptor in atheroma.
Legedz
Liliana
L
EA 3740, Faculté de médecine RTH Laennec, rue Guillaume Paradin, 69372 Lyon Cedex 08, France.
Randon
Jacques
J
Sessa
Carmine
C
Baguet
Jean-Philippe
JP
Feugier
Patrick
P
Cerutti
Catherine
C
McGregor
John
J
Bricca
Giampiero
G
D000368:Aged; D000369:Aged, 80 and over; D000808:Angiotensinogen / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000601:surgery; D017536:Carotid Artery, Common / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D002402:Cathepsin D / Q000378:metabolism; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism*; D016894:Endarterectomy, Carotid; D005260:Female; D005602:France; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012697:Serine Endopeptidases; D012720:Severity of Illness Index; D013223:Statistics as Topic; D016896:Treatment Outcome; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology / Q000601:surgery
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D002403:Cathepsins; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D002402:Cathepsin D