Isoform-specific immunolocalization of 14-3-3 proteins in atherosclerotic lesions of human carotid and main cerebral arteries

• Published in: Journal of the neurological sciences Vol. 317; no. 1; pp. 106 - 111
• Main Authors: Umahara, Takahiko, Uchihara, Toshiki, Koyama, Shunichi, Hashimoto, Takao, Akimoto, Jiro, Haraoka, Jo, Iwamoto, Toshihiko
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.06.2012; Elsevier
• Subjects: 14-3-3 protein; 14-3-3 proteins; 14-3-3 Proteins - metabolism; Aged; Aged, 80 and over; Antibodies; Apoptosis; Arteriosclerosis; Atherosclerosis; Biological and medical sciences; Carotid Arteries - immunology; Carotid Arteries - metabolism; Carotid Arteries - pathology; Carotid artery; Carotid Artery Diseases - metabolism; Carotid Artery Diseases - pathology; Cell survival; Cerebral Arteries - immunology; Cerebral Arteries - metabolism; Cerebral Arteries - pathology; Cerebral main artery; Differentiation; Endothelial cells; Female; Giant cells; Humans; Immunoreactivity; Intracranial Arteriosclerosis - metabolism; Intracranial Arteriosclerosis - pathology; Male; Medical sciences; Middle Aged; Neurology; Plaques; Protein Isoforms - metabolism; Smooth muscle; Tau protein; Thrombosis; Vascular diseases and vascular malformations of the nervous system; 14-3-3 proteins; Cerebral main artery; Carotid artery; Arteriosclerosis; Endothelial cells; Atherosclerosis; Human; Endothelial cell; Nervous system diseases; Cardiovascular disease; Cerebral artery; Protein; Vascular disease; Blood vessel; Carotid; Circulatory system
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2012.02.015

Abstract 14-3-3 proteins are now recognized to have a wide range of potential functions and pathological relevance, such as regulating the intercellular signal processes of differentiation, the development and growth of cells, or preventing or mediating cell apoptosis and survival by controlling the localization of potential signaling molecules. We investigated the immunolocalization of 14-3-3 proteins in atherosclerotic lesions of human cerebral and carotid arteries using 14-3-3 isoform-specific antibodies to distinguish 7 isoforms, and confirmed the cell type localization using double immunofluorolabeling. 14-3-3 common (COM)-like immunoreactivity (IR) was intense, mainly in the foam cells and multinucleated giant cells of the carotid artery. The beta, gamma, epsilon, tau, eta, and zeta (6/7) isoform-specific antibodies showed similar results to those with anti-14-3-3 COM antibody. However, among these isoform-specific antibodies, the anti-eta isoform antibody most intensely immunolabeled multinucleated giant cells and foam cells, and the anti-zeta isoform antibody most intensely immunolabeled infiltrating vascular smooth muscle cells (VSMCs), in carotid plaques. Zeta IR was also observed in one part of the mural thrombus and in the nuclei of foam cells. Gamma isoform-like IR was relatively limited in cell components, but extracellular lesions were partly positive for this isoform. In the main cerebral arteries, the anti-epsilon isoform antibody most intensely immunolabeled infiltrating VSMCs in the intima of thickened fibrous cap plaques. Endothelial cells were also positive for the epsilon isoform. These findings may provide a basis for understanding the isoform-specific role associated with atherosclerotic lesions of the cerebral and carotid arteries.