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 11 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 (AT(2)) 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 (AT,) 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, AT, receptor and ACE mRNAs. Angiotensinogen and cathepsin mRNAs and proteins were detected in both arterial layers. AT, immunoreactivity was mainly associated with alpha-actinpositive cells. Conclusion All components required for angiotensin 11 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 11 overproduction and contribute, with decreased number of differentiated smooth muscle cells, to the lower amount of AT, receptor in atheroma. (C) 2004 Lippincott Williams Wilkins.