Effects of atorvastatin and ezetimibe on endothelial function in dyslipidemic patients with chronic kidney disease

Backgroud

Chronic kidney disease (CKD) is a staple risk factor not only for renal failure but also for cardiovascular diseases. In addition, because dyslipidemia facilitates atherosclerosis and renal dysfunction, antihyperlipidemic treatment is important to prevent cardiac and renal events in CKD patients.

Methods

We compared the effects of a statin and an intestinal cholesterol transporter inhibitor in 20 dyslipidemic patients with CKD presenting with proteinuria and/or glomerular filtration rate <60 mL/min/1.73 m². Either 5–10 mg atorvastatin or 10 mg ezetimibe was given for 3 months each in a randomized crossover manner and the parameters of oxidative stress, inflammation and endothelial function were compared.

Results

Atorvastatin lowered serum low-density lipoprotein (LDL) cholesterol more prominently than ezetimibe (103 ± 38 vs 130 ± 45 mg/dL, p < 0.001), while serum γ-glutamyl transpeptidase was higher in atorvastatin than in ezetimibe (29 ± 16 vs 25 ± 11 U/L, p = 0.013). On the other hand, serum oxidized LDL and high-sensitivity C-reactive protein were lower in the atorvastatin treatment period than in the ezetimibe treatment period (109 ± 38 vs 146 ± 67 U/L, p = 0.002; 1.02 ± 1.46 vs 1.47 ± 1.77 µg/mL, p = 0.003). Although serum adiponectin was not significantly different between the two drugs, the reactive hyperemia index, an index of endothelial function, was higher in atorvastatin than in ezetimibe (1.94 ± 0.58 vs 1.60 ± 0.44, p = 0.023).

Conclusion

It is concluded that atorvastatin is more potent than ezetimibe in improving the serum lipid profile, reducing oxidative stress, suppressing inflammation and preserving endothelial function, while ezetimibe may be advantageous in reducing the hepatic lipid load.     

Interleukin-4 and interleukin-5 map to human chromosome 5 in a region encoding growth factors and receptors and are deleted in myeloid leukemias with a del(5q)

Interleukin-4 (IL-4) is a potent mediator of growth and differentiation of cells of several hematopoietic lineages. Interleukin-5 (IL-5) is a lineage-specific hematopoietic growth factor that stimulates the production of eosinophils and eosinophil colonies from normal human bone marrow cells. By using somatic cell hybrids and in situ chromosomal hybridization, we localized the IL-4 and IL-5 genes to human chromosome 5 at bands q23-31, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, the IL-4 and IL-5 genes were found to be deleted in the 5q- chromosome of four patients with refractory anemia (RA) or therapy-related acute nonlymphocytic leukemia (t-ANLL), who had a del(5q). Thus a small segment of chromosome 5 contains IL-4, IL-5, IL- 3, and GM-CSF as well as other genes such as CD14 and EGR1. Our findings that each of these genes was deleted in the 5q- chromosome suggest that loss of function of one or more of these genes may play an important role in the pathogenesis of hematologic disorders associated with a del(5q).     

Ultrastructural localization of human platelet thrombospondin, fibrinogen, fibronectin, and von Willebrand factor in frozen thin section

We have investigated the localization of thrombospondin (TSP), fibrinogen, fibronectin, and von Willebrand factor in human platelets by transmission electron microscopy of antibody-stained ultrathin frozen sections. In negatively stained thin sections, alpha granules were identified on the basis of their smooth, roughly spherical shape, size, single limiting electron-lucent 100 A membrane, and frequent presence of electron-dense nucleoid. In contrast, mitochondria exhibited characteristic double membranes and cristae. Sections were separately stained with affinity-purified polyclonal antibodies to these proteins as well as with three monoclonal anti-TSP antibodies. Antibody specificity was documented in radioimmunoassays, by immunofluorescent cross-blocking, and by staining of bands of appropriate mobility in Western blots of whole platelets. Bound antibody was visualized using a 5-nm colloidal gold-avidin conjugate. In resting cells, staining of virtually all alpha granules was observed for all four proteins. In contrast, consistent staining was absent from other organelles, including plasma membranes, mitochondria, and vacuolar structures that may represent the open canalicular system.