Induction of CCN1 in Growing Saccular Aneurysms: A Potential Marker Predicting Unstable Lesions

• Published in: Journal of neuropathology and experimental neurology 2021-07, Vol.80 (7), p.695-704
• Main Authors: Shimizu, Kampei, Imai, Hirohiko, Kawashima, Akitsugu, Okada, Akihiro, Ono, Isao, Miyamoto, Susumu, Kataoka, Hiroharu, Aoki, Tomohiro
• Format: Article
• Language: English
• Subjects: Analysis; Aneurysms; Animals; Biological markers; Biomarkers - metabolism; Cellular proteins; Cysteine-Rich Protein 61 - genetics; Cysteine-Rich Protein 61 - metabolism; Development and progression; Diagnosis; Health aspects; Humans; Immunohistochemistry; Intracranial Aneurysm - metabolism; Intracranial Aneurysm - pathology; Intracranial aneurysms; Macrophages - metabolism; Male; Myocytes, Smooth Muscle - metabolism; Neurological research; Proteins; Rats; Rats, Sprague-Dawley; Up-Regulation
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1093/jnen/nlab037

Abstract Growing evidence has suggested that inflammatory responses promote the progression of saccular intracranial aneurysms (IAs). However, a biomarker predicting the progression has yet to be established. This study aimed to identify novel molecules upregulated during the progression using a previously established rat aneurysm model. In this model, aneurysms are induced at the surgically created common carotid artery (CCA) bifurcation. Based on sequential morphological data, the observation periods after the surgical manipulations were defined as the growing phase (on the 10th day) or the stable phase (on the 30th day). Total cell lysates from the CCA with or without an aneurysm lesion were prepared to perform protein array analysis. The protein array analysis revealed that the matricellular protein cellular communication network factor 1 (CCN1) is induced in lesions during the growing phase. Immunohistochemistry corroborated the significant upregulation of CCN1 in the growing phase compared with the stable phase. Simultaneously with the induction of CCN1, significant increases in the number of CD68-positive macrophages, myeloperoxidase-positive cells, and proliferating smooth muscle cells in lesions were observed. Immunohistochemistry of human IA specimens reproduced the induction of CCN1 in some lesions. These findings imply a potential role of CCN1 as a marker predicting the progression of saccular aneurysms.