Direct relationship between cell density and FDG uptake in asymptomatic aortic aneurysm close to surgical threshold: an in vivo and in vitro study.

PURPOSE: Conflicting results have been reported about the clinical value of fluorodeoxyglucose (FDG) imaging in predicting the risk of rupture of abdominal aortic aneurysm (AAA). The present study tests the hypothesis that FDG uptake is low in asymptomatic noninflammatory AAA due to the low cell density in aneurysmal walls. METHODS: Positron emission tomography (PET)/CT imaging was performed in 12 consecutive candidates for AAA surgical repair and in 12 age- and sex-matched controls. At intervention, aneurysmal walls were cut into three sequential blocks. Block A was frozen to cut three 5-µm slices for incubation with 2-3 MBq of FDG for 5 min. Block C was first incubated with the same tracer solution for the same time and subsequently frozen to cut three 5-µm slices. Autoradiographic images were coregistered with immunohistochemical pictures of cell density, type and DNA synthesis as assessed on block B. RESULTS: No visible uptake in abdominal aorta occurred in any patient or control subject. Immunohistochemistry documented a severe loss of wall structure, with low numbers of cells. Tracer retention directly correlated with overall cell density and with prevalence of cells synthesizing DNA. The metabolic nature of FDG uptake was confirmed by the selective effect of preliminary freezing that decreased tracer content by 90% in regions with high cell density and only by 34% in cold acellular areas. CONCLUSION: The loss of tissue structure and the marked decrease in cell density account for the low prevalence of positive findings at FDG PET imaging, at least in asymptomatic patients bearing AAAs whose diameter is close to surgical indication.

Diabetes impairs the vascular recruitment of normal stem cells by oxidant damage, reversed by increases in pAMPK, heme oxygenase-1, and adiponectin.

BACKGROUND: Atherosclerosis progression is accelerated in diabetes mellitus (DM) by either direct endothelial damage or reduced availability and function of endothelial progenitor cells (EPCs). Both alterations are related to increased oxidant damage. AIM: We examined if DM specifically impairs vascular signaling, thereby reducing the recruitment of normal EPCs, and if increases in antioxidant levels by induction of heme oxygenase-1 (HO-1) can reverse this condition. METHODS: Control and diabetic rats were treated with the HO-1 inducer cobalt protoporphyrin (CoPP) once a week for 3 weeks. Eight weeks after the development of diabetes, EPCs harvested from the aorta of syngenic inbred normal rats and labeled with technetium-99m-exametazime were infused via the femoral vein to estimate their blood clearance and aortic recruitment. Circulating endothelial cells (CECs) and the aortic expression of thrombomodulin (TM), CD31, and endothelial nitric oxide synthase (eNOS) were used to measure endothelial damage. RESULTS: DM reduced blood clearance and aortic recruitment of EPCs. Both parameters were returned to control levels by CoPP treatment without affecting EPC kinetics in normal animals. These abnormalities of EPCs in DM were paralleled by reduced serum adiponectin levels, increased numbers of CECs, reduced endothelial expression of phosphorylated eNOS, and reduced levels of TM, CD31, and phosphorylated AMP-activated protein kinase (pAMPK). CoPP treatment restored all of these parameters to normal levels. CONCLUSION: Type II DM and its related oxidant damage hamper the interaction between the vascular wall and normal EPCs by mechanisms that are, at least partially, reversed by the induction of HO-1 gene expression, adiponectin, and pAMPK levels.