Contribution of angiotensin-converting enzyme and angiotensin II to ischemic stroke: their role in the formation of stable and unstable carotid atherosclerotic plaques.

Background: The angiotensin-converting enzyme/angiotensin II (ACE/Ang II) system is a strong contributor to intimal hyperplasia in atherosclerotic lesions. To illuminate its role in ischemic stroke, we examined the expression of ACE/Ang II in stable and unstable carotid atherosclerotic plaques from symptomatic and asymptomatic patients.

Methods: Using immunohistochemical methods, we studied differences between carotid atherosclerotic lesions obtained at carotid endarterectomy (CEA) from symptomatic (n = 36) and asymptomatic (n = 28) patients. The specimens were classified as stable (n = 30) and unstable (n = 34) plaques, and their fibrous cap, lipid core, and shoulder lesion were examined. We used antibodies against smooth muscle cells (SMC), macrophages, endothelial cells (EC), ACE, and Ang II.

Results: Of 28 lesions from asymptomatic patients, 20 (71.4%) manifested features characteristic of stable plaques: the expression of ACE/Ang II co-localized with SMC, EC, and macrophages in the shoulder lesion. In contrast, 26 of 36 symptomatic lesions (72.2%) exhibited the typical features of unstable plaques: dense accumulations of macrophages near the luminal surface in the shoulder lesion and weak immunoreactivity for ACE/Ang II, EC, and SMC. Furthermore, most of the lesions were accompanied by early stage atherosclerotic lesions (satellite lesions) that were strongly immunoreactive with macrophages, EC, and ACE/Ang II.

Conclusions: ACE/Ang II expression may induce the proliferation of SMC and EC and result in the formation of carotid atherosclerotic plaques with a thick fibrous cap. Notably, the shoulder lesion of unstable plaques exhibited a thin fibrous cap and faintly expressed ACE/Ang II. Lack of the ACE/Ang II system may contribute to the final step in plaque rupture.