Kruppel-like Zinc-Finger Transcription Factor 5 (KLF5) Is Highly Expressed in Large and Giant Unruptured Cerebral Aneurysms

BACKGROUND: Kruppel-like zinc-finger transcription factor 5 (KLF5), known as BTEB2 and IKLF, has several biological functions that involve cell proliferation, development, and apoptosis. In human cerebral aneurysms, macrophage infiltration is profoundly associated with growth and rupture, but the role of KLF5 remains unclear. We examined the significance of KLF5 expression in cerebral aneurysms. METHODS: Unruptured (n = 15) and ruptured (n = 12) aneurysms obtained at surgery or autopsy were divided into 3 size groups: small (<10 mm); large (>= 10 mm but <25 mm); and giant (>= 25 mm). Control samples comprised 5 cerebral arteries obtained from surgery or autopsy subjects. The expression of KLF5-, alpha-smooth muscle actin-, and KP-1 (macrophages) -positive cells were counted and compared between groups. RESULTS: Media of control arteries was negative for KLF5. In the luminal layers, KLF5 in unruptured small aneurysm was also negative; KLF5 expression was higher in unruptured large/giant aneurysms than other groups (P < 0.05). KP-1 expression in unruptured large/giant aneurysms, ruptured small aneurysms, and ruptured large/giant aneurysms was higher than in unruptured small aneurysms (P < 0.05). In the unruptured large/giant aneurysms, KP-1-positive cells were lower than KLF5-positive cells. On the other hand, irrespective of size, KLF5 positivity tended to be lower than KP-1 in the luminal and abluminal layers of all ruptured aneurysms. CONCLUSIONS: This represents the first documentation that KLF5 is highly expressed in large and giant unruptured aneurysms and that in ruptured aneurysmal wall KLF5 expression was scarce. These findings suggest that the KLF5 expression and macrophage infiltration play essential roles on aneurysmal growth or rupture.