Increased apoptosis and cysteinyl aspartate specific protease-3 gene expression in human intracranial aneurysm

Objective: To investigate apoptosis in vascular smooth muscle cells (VSMCs) and caspase-3 expression in ruptured intracranial aneurysm. Methods: Tissue samples of 15 ruptured intracranial aneurysms, 6 abdominal aortic aneurysms (AAA) and 6 normal vessels were evaluated. Apoptosis in VSMCs was determined on transmission electron microscopy. Immunohistochemistry for alpha-SMC actin and direct cell counts (medial VSMCs per high-power field (HPF)) were employed to determine medial VSMC density. Additionally, gene expression of caspase-3 was determined using real-time RT-PCR. Results: We demonstrated medial VSMCs exhibiting morphological apoptotic changes in cerebral aneurysm and AAA. Medial VSMC density was significantly decreased in intracranial aneurysm (43.9 +/- 4.3 SMCs/HPF) and AAA (53.2 +/- 9.4 SMCs/HPF) compared with the normal arteries (222.8 +/- 12.1 SMCs/HPF-, p < 0.01). An 8.94-fold and 6.73-fold increase in expression of caspase-3mRNA in intracranial aneurysm and AAA, respectively, were obtained relative to the normal vessels. Conclusions: These results suggest that real time RT-PCR provides a useful tool to test gene expression in small samples, and may contribute to a better understanding of the role of apoptosis in ruptured intracranial aneurysm. (c) 2005 Elsevier Ltd. All rights reserved.