thymosin and Hypercholesterolemia

Translations of new therapeutic options for cardiovascular disease from animal studies into a clinical setting have been hampered, in part by an improper reflection of a relevant patient population in animal models. In this study, we investigated the impact of thymosin β4 (Tβ4), which promotes collateralization and capillarization, during hypercholesterolemia, a known risk factor of coronary artery disease. Initial in vitro results highlighted an improved endothelial cell function upon Tβ4 treatment under control conditions and during hypercholesterolemic stress (scratch area [pixels]: oxidized low-density lipoprotein [oxLDL], 191,924 ± 7,717; and oxLDL + Tβ4, 105,621 ± 11,245). To mimic the common risk factor of hypercholesterolemia in vivo, pigs on regular (NC) or high-fat (HC) diet underwent chronic myocardial ischemia followed by recombinant adeno-associated virus (rAAV)-mediated transduction of Tβ4 or LacZ as a control. We show that Tβ4 overexpression improves capillarization and collateralization (collaterals: NC + rAAV.LacZ, 2.1 ± 0.5; NC + rAAV.Tβ4, 6.7 ± 0.5; HC + rAAV.LacZ, 3.0 ± 0.3; and HC + rAAV.Tβ4, 6.0 ± 0.4), ultimately leading to an improved myocardial function in both diet groups (ejection fraction [EF] at day 56 [%]: NC + rAAV.LacZ, 26 ± 1.1; NC + rAAV.Tβ4, 45 ± 1.5; HC + rAAV.LacZ, 26 ± 2.5; and HC + rAAV.Tβ4, 41 ± 2.6). These results demonstrate the potency of Tβ4 in a patient-relevant large animal model of chronic myocardial ischemia.

Topics: Animals; Dependovirus; Disease Models, Animal; Endothelial Cells; Hypercholesterolemia; Lipoproteins, LDL; Myocardial Ischemia; Myocardium; Neovascularization, Physiologic; Swine; Thymosin

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

Thymosin alpha-1 is an active polypeptide isolated from thymus. This polypeptide is widely used in the diagnosis and treatment of many diseases, especially immune diseases. In this present study, we examined the effects of thymosin alpha-1 on plasma and erythrocyte lipid levels and the changes in erythrocyte membrane (Na+, K+)ATPase activity in hypercholesterolemic rabbits. The erythrocyte lipid levels decreased, whereas the erythrocyte membrane (Na+, K+)ATPase activity increased significantly in these rabbits after thymosin alpha-1 injection. These findings suggest that thymosin alpha-1 is effective on both the lipid level and erythrocyte membrane (Na+, K+)ATPase activity.

Topics: Animals; Erythrocyte Membrane; Hypercholesterolemia; Lipids; Rabbits; Sodium-Potassium-Exchanging ATPase; Thymalfasin; Thymosin

New Zealand White rabbits were made hypercholesterolemic by feeding a high cholesterol diet (20 g/kg diet) for 3 months. Plasma cholesterol concentrations were monitored as a function of time. At the end of 3 months, the plasma lipid levels, the whole blood, erythrocyte and haemoglobin-bound 2,3-DPG levels and leucocyte counts increased, whereas erythrocyte counts, hematocrit and haemoglobin levels decreased significantly in hypercholesterolemic rabbits. At the end of 3 months, the rabbits in the experimental group were divided into two groups. The first group was fed a standard diet for 21 days. The second group received 0.5 mg/kg thymosin F5 injection i.p. every other day for 21 days. After this period, the plasma lipid levels, the whole blood, erythrocyte and haemoglobin-bound 2,3-DPG levels, erythrocyte and leucocyte counts, hematocrit and haemoglobin levels were measured. Rabbits fed diets supplemented with thymosin F5 had markedly lower plasma lipid levels, erythrocyte counts, hematocrit and haemoglobin levels and enhanced leucocyte counts, but did not have significantly less whole blood, erythrocyte and haemoglobin-bound 2,3-DPG levels. We conclude that thymosin F5 has lipid-lowering effects in hypercholesterolemic rabbits. The data further suggest that effects of thymosin F5 on haematological parameters are due to the cholesterol decrease and not to the direct regulatory mechanism.

Topics: 2,3-Diphosphoglycerate; Anemia; Animals; Blood Cell Count; Cattle; Cholesterol; Diet; Diphosphoglyceric Acids; Hemoglobins; Hypercholesterolemia; Lipids; Rabbits; Thymosin

The effect of thymosin F5 injection on the erythrocyte glutathione levels were investigated in the rabbits fed 2% cholesterol diet for 4 weeks. Although the cholesterol rich diet caused a significant decrease in erythrocyte glutathione levels, erythrocyte lipid peroxide levels were increased considerably. After a cholesterol-rich diet, the rabbits were injected thymosin F5 (0.5 mg/kg body weight, i.p) every other day for 21 days. Thymosin F5 treatment caused a significant increase in erythrocyte glutathione levels. However erythrocyte lipid peroxide levels decreased significantly. These findings suggest that thymosin F5 is effective on both the glutathione concentration and the propagation of lipid peroxidation in red blood cells.

Topics: Animals; Cattle; Cholesterol; Diet, Atherogenic; Erythrocytes; Glutathione; Hypercholesterolemia; Lipid Peroxides; Rabbits; Thymosin

Plasma and erythrocyte lipid levels and susceptibility of erythrocytes to lipid peroxidation were determined in rabbits fed diet containing 2% (w/w) cholesterol, for 3 months. Hypercholesterolemic rabbits had high plasma and erythrocyte lipid peroxide levels as compared to control rabbits. After high-cholesterol diet, the rabbits in the experimental group were divided into two groups. The first group was fed a normal diet for 21 days and the second group was given normal diet plus thymosin F5 injections every other day for the same period. At the end of this period, plasma and erythrocyte lipid peroxide levels were significantly decreased in the group injected with thymosin F5.

Topics: Animals; Cholesterol; Cholesterol, Dietary; Erythrocytes; Hypercholesterolemia; Lipid Peroxidation; Lipid Peroxides; Rabbits; Reference Values; Thymosin; Triglycerides

The effects of thymus fraction 5 injection on cholesterol, triglyceride and phospholipid levels in plasma and erythrocytes as well as on membrane-bound (Na+ + K+)-ATPase activity were investigated in rabbits fed a high-cholesterol diet for 3 months. While cholesterol feeding caused an increase in plasma and erythrocytes phospholipid levels, (Na+ + K+)-ATPase activity was found to be reduced. After high-cholesterol diet, the rabbits were given normal diet with or without thymosin F5 injections every other day for 21 days. Thymosin F5 treatment caused a significant decrease in plasma and erythrocyte phospholipid levels whereas membrane-bound (Na+ + K+)-ATPase activity was increased significantly. It is concluded that hypercholesterolemic lesions and the decreased erythrocyte ATPase activity may be eliminated by thymic extracts in rabbits.

Topics: Animals; Cholesterol; Diet, Atherogenic; Erythrocytes; Hypercholesterolemia; Phospholipids; Rabbits; Sodium-Potassium-Exchanging ATPase; Thymosin; Triglycerides