The study demonstrates that while ACE expression is prominent in macrophages of de-novo coronary lesions, in-stent restenotic lesions are characterized by young vascular smooth muscle cells abundantly expressing AT1 receptors.
Supports divergent RAS involvement by lesion type; hypothesis-generating for targeted therapies, not yet practice-changing.
OBJECTIVE: Different components of the renin-angiotensin system (RAS) have been demonstrated in atherosclerotic plaques. However, the involvement of the RAS in in-stent restenosis is not clear. We studied the differential immunolocalisation of angiotensin converting enzyme (ACE) and the angiotensin II type 1 (AT1) receptor in de-novo stenotic lesions and in-stent restenotic lesions in human coronary arteries. METHODS: Using a pullback atherectomy catheter, biopsies from de-novo coronary lesions (n=19) and in-stent restenotic lesions (n=19) were obtained. The biopsies were immunostained for vascular smooth muscle cells (VSMCs), macrophages, ACE and the AT1 receptor. RESULTS: In biopsies from de-novo stenotic lesions ACE-positive macrophages were more numerous than in in-stent restenotic lesions (P=0.002). Moreover, in the latter lesions, ACE-positive macrophages decreased when the time interval of stent implantation was longer. On the other hand, in-stent restenotic lesions contained predominantly young VSMCs, which abundantly expressed AT1 receptors. CONCLUSIONS: Lesional ACE expression is not a prominent feature of in-stent restenotic lesions. In contrast, AT1 receptors are abundantly expressed on young VSMCs. In de-novo lesions ACE and AT1 receptors were found on macrophages and VSMCs, which were present in all specimens.
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Lodewijk J. Wagenaar (2003) studied this question.
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