Lack of cell stress markers in fibrous cap cells in the left main coronary artery

Abstract

Fibrous cap formation is a key aspect of preventing clinical events but animal models to study this are limited and cellular stress plays a fundamental role in fibrous cap formation. Aims: To characterise cellular stress markers in an established animal model to study coronary artery fibrous cap formation. Methods: Male New Zealand White rabbits were fed a diet containing 0.5% cholesterol and 1% methionine for 4 weeks, then 9 weeks of normal diet to induce fibrous cap formation. Immunohistochemistry was used to detect CHOP, GRP78, nitrotyrosine HSP70, HSP90, iNOS and HSP32. Results: The core within the left main coronary artery atherosclerosis contained vast amount of foamy macrophages which readily stained for all markers. However, the smooth muscle cells within the formed fibrous cap were negative for all markers. The endothelium overlying the fibrous cap was positive for CHOP, GRP78, nitrotyrosine, iNOS and HSP32, however it was difficult to detect positive endothelial HSP70 or HSP90 immunoreactivity. Serial sectioning and immunohistochemistry for all factors showed clear dual iNOS+ / HSP32+ / HSP70- / HSP90- single cells within the fibrous cap formed. Conclusion: Smooth muscle cells within fibrous caps appear ‘stress free’, however isolated single smooth muscle cells within caps and within the core show positive immunoreactivity for stress markers. This model could be used to understand the role of cellular stress in fibrous cap formation in the coronary artery.