Emeossigenasi-1 nella prevenzione della ristenosi post-angioplastica: effetti della biliverdina e del monossido di carbonio

In humans, vascular proliferative diseases resulting in narrowing of vessels are one of the world’s leading causes of mortality. Heme oxygenase (HO-1) provides a cellular defense mechanism during oxidative stress and catalyzes the rate-limiting step in heme metabolism that produces biliverdin (BV), carbon monoxide (CO) and iron. Recently it has been demonstrate that HO-1 acts as anti-inflammatory and anti-apoptotic gene (1) and this presumably may contribute to suppress deleterious effects associated with rejection of transplanted organs, endotoxemia and hyperoxia. In humans, there are evidences supporting the association of high normal levels of bilirubin with fewer atherosclerotic-related disorders as compared with individuals with low normal levels (2, 3). In this study we hypothesize that systemic/local administration of biliverdin or inhalation of 250 ppm of CO could prevent restenosis of the arteries after angioplasty application and may have use in atherosclerosis prevention therapy. Adult male (400-500g) Sprague Dowley rats were used in this balloon injury model. Rats were anesthetized (ketamine and tiletamine/zolazepam, i.p.), and the right common carotid artery (CA) was exposed. After obtaining proximal and distal vascular control, a 2-French arterial embolectomy catheter was inserted, and injury was created by inflating the balloon; then the blood flow was reestablished. Animals were euthanized 14 days after surgery, and the CAs were collected and snap-frozen. Samples were sectioned (5 μm thick) in every 200 μm distance, and were stained with hematoxylin-eosin or with Verhoeff’s Van Gieson.