Inactivation of the Lysyl Oxidase Gene Lox Leads to Aortic Aneurysms, Cardiovascular Dysfunction, and Perinatal Death in Mice

TLDR: Lox has an essential role in the development and function of the cardiovascular system and inactivation of the Lox gene causes structural alterations in the arterial walls, leading to abnormalities in the cardiovascular functions.

Abstract: Background— The lysyl oxidases are extracellular copper enzymes that initiate the crosslinking of collagens and elastin, 5 human isoenzymes having been characterized so far. The crosslinks formed provide the tensile strength and elastic properties for various extracellular matrices, including vascular walls. We studied the role of the first described isoenzyme Lox by inactivating its gene in mice. Methods and Results— Murine Lox gene was disrupted by routine methods. Lox−/− mice died at the end of gestation or as neonates, necropsy of the live-born pups revealing large aortic aneurysms. In light microscopy, hazy and unruffled elastic lamellae in the Lox−/− aortas were observed, and electron microscopy of the aortic walls of the Lox−/− fetuses showed highly fragmented elastic fibers and discontinuity in the smooth muscle cell layers in Lox−/− fetuses. The wall of the aorta in the Lox−/− fetuses was significantly thicker, and the diameter of the aortic lumen was significantly smaller than that in the Lox+/+...