thymosin and Arteriosclerosis

Transplant arteriosclerosis is the result of intima proliferation in large vessels upon organ transplantation. Obliteration of the vascular lumen will ultimately lead to ischemia and late graft failure. Gene array analysis was performed to identify factors involved in the pathogenesis of transplant arteriosclerosis. Aortic transplants from Dark Agouti to Wistar Furth rats were performed to identify potential target genes. Hierarchical clustering of genes specifically upregulated in allogeneic but not in syngeneic aortas revealed 19 genes. A gene that fulfilled these criteria is prothymosin alpha (PTMA), a regulator of estrogen receptor transcriptional activity. PTMA gene and protein expression levels were confirmed by PCR and immunohistochemistry. Estrogen receptor staining was increased in allogeneic aortas. Furthermore, cyclin D1 a downstream target of PTMA, was also up regulated in allogeneic aortas. In conclusion, PTMA was identified as potential candidate gene involved in transplant arteriosclerosis.

Topics: Animals; Aorta; Arteriosclerosis; Cyclin D1; Gene Expression Profiling; Immunohistochemistry; Male; Polymerase Chain Reaction; Protein Precursors; Rats; Rats, Inbred WF; Thymosin; Transplantation, Homologous

VPF/VEGF acts selectively on the vascular endothelium to enhance permeability, induce cell migration and division, and delay replicative senescence. To understand the changes in gene expression during endothelial senescence, we investigated genes that were differentially expressed in early vs. late passage (senescent) human dermal endothelial cells (HDMEC) using cDNA array hybridization. Early passage HDMEC cultured with or without VPF/VEGF overexpressed 9 and underexpressed 6 genes in comparison with their senescent counterparts. Thymosin beta-10 expression was modulated by VPF/VEGF and was strikingly down-regulated in senescent EC. The beta-thymosins are actin G-sequestering peptides that regulate actin dynamics and are overexpressed in neoplastic transformation. We have also identified senescent EC in the human aorta at sites overlying atherosclerotic plaques. These EC expressed senescence-associated neutral beta-galactosidase and, in contrast to adventitial microvessel endothelium, exhibited weak staining for thymosin beta-10. ISH performed on human malignant tumors revealed strong thymosin beta-10 expression in tumor blood vessels. This is the first report that Tbeta-10 expression is significantly reduced in senescent EC, that VPF/VEGF modulates thymosin beta-10 expression, and that EC can become senescent in vivo. The reduced expression of thymosin beta-10 may contribute to the senescent phenotype by reducing EC plasticity and thus impairing their response to migratory stimuli.

Topics: Actins; Adenocarcinoma; Aorta, Thoracic; Arteriosclerosis; Cells, Cultured; Cellular Senescence; Colonic Neoplasms; DNA, Complementary; Endothelial Growth Factors; Endothelium, Vascular; Gene Expression Regulation; Humans; Infant, Newborn; Lymphokines; Male; Microcirculation; RNA, Messenger; Skin; Thymosin; Transcription, Genetic; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

In the present study, the effects of thymosin alpha1 on lipid peroxidation were studied in an in vivo model of experimental hypercholesterolemia. In groups II-IV, rabbits were fed a high-cholesterol diet 2% (w/w) for 10 weeks. Thereafter, rabbits in group III were fed a normal diet for another 14 days and those in group IV were given a normal diet plus 25 microg/kg thymosin alpha1 intraperitoneally every other day for the same period. At the end of this period, plasma and erythrocyte lipid levels and susceptibility of erythrocytes to lipid peroxidation were determined in all groups. Hypercholesterolemic rabbits had high plasma and erythrocyte lipid peroxide (TBARS) levels compared to control animals fed a normal diet. Plasma and erythrocyte TBARS levels significantly decreased in the thymosin-alpha1-injected rabbits. In thymosin-alpha1-treated animals (group IV), most of the lipid plaques were replaced by fibrous tissue. These findings suggest that thymosin alpha1 may have some beneficial effects on the treatment of atherosclerosis by normalizing blood lipid levels and by substantially protecting endothelial cells against free radical injury.

Topics: Animals; Aorta; Arteriosclerosis; Cholesterol, Dietary; Cholesterol, HDL; Erythrocytes; Hypercholesterolemia; Lipid Peroxidation; Lipids; Rabbits; Thiobarbituric Acid Reactive Substances; Thymosin

The thymus hormones were reported to be effective on lipid peroxidation and the antioxidant system. Thymus plays a broader role than just regulating the immune system. Thymosin alpha 1 is the first subgroup extracted from thymosin F5 and has higher biological activity than thymosin F5. In the present study, we have examined the effects of thymosin alpha 1 on lipid levels and lipid peroxidation and glutathione (GSH) content in the plasma, liver and aorta tissues of atherosclerotic rabbits. At the end of thymosin alpha 1 treatment, we determined the lipid levels and lipid peroxidation of the plasma, liver and aorta tissues and hepatic subcellular fractions in these rabbits. Our results demonstrated that thymosin alpha 1 might normalize changed lipid levels and increased lipid peroxides and also elevate decreased GSH in the plasma, liver and aorta tissues of atherosclerotic rabbits. Results of this study suggest that thymosin alpha 1 may be beneficial to prevent and/or to treat atherosclerosis.

Topics: Animals; Antioxidants; Aorta; Arteriosclerosis; Cholesterol, Dietary; Lipid Peroxidation; Liver; Malondialdehyde; Oxidative Stress; Rabbits; Thymalfasin; Thymosin

Topics: Animals; Aorta; Arteriosclerosis; Collagen; Elastin; Glycosaminoglycans; Male; Rabbits; Thymosin