Abstract WP134: Expression of Nox4 and Nox5 are Associated with Carotid Vulnerable Atherosclerotic Plaque in a Swine Model

Abstract

Purpose: Fibrous cap rupture from atherosclerotic plaque can send distal emboli and lead to stroke in patients with carotid disease. The NADPH oxidases (Nox) family play an important role in the pathophysiology of atherosclerosis. However, the relationship of Nox expression with atherosclerotic plaque vulnerability remain elusive. We aim to assess the association of Nox4 and Nox5 expression with carotid plaque vulnerability in a swine model. Methods: Carotid atherosclerosis was induced in miniswines using partial ligation and high cholesterol diet, and a minimum 70% stenosis was confirmed by Doppler ultrasonography. Carotid artery sections were obtained for histologic examination and immunohistochemical study for Nox4 and Nox5 at 3 months. The atherosclerotic lesions of AHA type IV to VI were defined as advanced plaques. The association of Nox4 and Nox5 expression in the plaque with the feature of plaque vulnerability was analyzed. Results: Seventy-five carotid segments from ten carotid artery models had fibrous cap plaques with AHA type IV to VI. Distal embolism with the presence of atheroemboli was found in all rete mirabilis, and deemed to be from the ipsilateral carotid plaques. Positive staining of Nox4 and Nox5 were mostly distributed in the surrounding of lipid core, endothelium and plaque shoulder. Increased expression of Nox4 in the plaque was associated with the features of a large lipid core, marked foam cell and thin fibrous cap (p<0.01). Overexpression of Nox5 in the plaque was associated with marked foam cell and cap rupture (p<0.05). Co-overexpression of Nox4 and Nox 5 in the plaque was associated with thin cap (p<0.05). Low expression of both Nox4 and Nox5 in the plaque was associated with less thin cap and less cap rupture (p<0.01). There was a higher frequency of thin cap and cap rupture in 27 plaques with co-overexpression of Nox4 and Nox 5 than in 26 plaques with low expression of both Nox4 and Nox5. Conclusion: Nox4 and Nox5 are both expressed in carotid atherosclerotic plaques in a swine model, and their overexpression in carotid plaques are associated with thin fibrous cap and cap rupture. Upregulated Nox4 and Nox5 may participate in the process of vulnerable atherosclerotic plaque and may be used as a target for reducing the risk of distal embolism.