Inflammation and atherosclerosis – activation of proapoptotic stress-pathway "unfolded protein response" in plaques of the internal carotid artery

• Published in: The Thoracic and Cardiovascular Surgeon
• Main Authors: Dorweiler, B, Grechowa, I, Wallrath, A, Horke, S, Vahl, CF
• Format: Conference Proceeding
• Language: English
• Published: 23.01.2013
• ISSN: 0171-6425; 1439-1902
• DOI: 10.1055/s-0032-1332457

Objective: Proinflammatory stimuli play a key role in progression of atherosclerotic lesions and increased apoptotic load is seen as one of the triggers of plaque rupture. The intracellular stress pathway “unfolded protein response” (UPR) has the potential to induce apoptosis in macrophages as well as smooth muscle cells and endothelial cells. Aim of the study was to investigate activation of the UPR in plaque material. Methods: Plaque material was obtained during carotid endarterectomy, formalin-fixed and embedded in paraffin. Plaques were then completely cut and representative sections were stained for histology and immunohistochemistry. To assess activation of the UPR, key elements like GRP78, KDEL, ATF3 and CHOP were analyzed. In addition, markers of cellular infiltration (macrophages, granulocytes) and apoptosis (TUNEL) were studied. Results: Analysis of markers for macrophages and granulocytes revealed an increased presence of both cell types in symptomatic lesions. In addition, upregulation of the UPR was seen by increased expression of signal molecules like GRP78, ATF3 and CHOP. Colocalization studies showed activation of UPR in immigrated macrophages as well as intimal smooth muscle cells. Conclusion: Activation of proinflammatory and proapoptotic signaling is a key feature of progression of atherosclerotic lesions. Upregulation of the proapoptotic signaling pathway “unfolded protein response” in plaques of the internal carotid artery represents a new finding that may provide evidence for increased aopototic load.