thymosin and Obesity

Endothelial progenitor cells (EPCs) are bone-marrow derived cells that are critical in the maintenance of endothelial wall integrity and protection of ischemic myocardium through the formation of new blood vessels (vasculogenesis) or proliferation of pre-existing vasculature (angiogenesis). Diabetes mellitus (DM) and the metabolic syndrome are commonly associated with ischemic heart disease through its pathological effects on the endothelium and consequent endothelial dysfunction. Thymosin-β4 (Tβ4) which expressed in the embryonic heart is critical in epicardial and coronary artery formation. In this study, we explored the effects of Tβ4 treatment on diabetic EPCs in vitro and intramyocardial injection of Tβ4-treated and non-Tβ4 treated EPCs following acute myocardial infarction (MI) of diabetic rats in vivo. It was found that 10 ng/mL Tβ4 increased migration, tubule formation, and angiogenic factor secretion of diabetic EPCs in vitro. In vivo, although implantation of Tβ4 treated diabetic EPCs significantly increased capillary density and attracted more c-Kit positive progenitor cells into the infarcted hearts as compared with implantation of non-Tβ4 treated diabetic EPCs, the significantly improved left ventricular ejection fraction was only found in the rats which received non-Tβ4 treated EPCs. The data suggests that a low dose Tβ4 increases diabetic EPC migration, tubule formation, and angiogenic factor secretion. However, it did not improve the effects of EPCs on left ventricular pump function in diabetic rats with MI.

Topics: Animals; Diabetes Mellitus, Experimental; Disease Models, Animal; Echocardiography; Endothelial Progenitor Cells; Humans; Male; Microfilament Proteins; Myocardial Infarction; Obesity; Rats; Rats, Zucker; Thymosin

Experiment 1 involved genetically lean and obese gilts and barrows injected for 42 d with 0, 2, or 4 mg/d of porcine somatotropin (pST; n = 96). Blood was collected at 0, 6, and 24 h after the initial pST injection and thereafter every 2 wk. Experiment 2 involved lean and obese gilts and barrows (n = 48) that were administered implants that released 0, 2, or 4 mg/d of pST for 42 d. Blood was collected at d 0, 7, 14, 28, and 42 of the study. Thymic weights and a final blood sample were collected at the end of the 42-d trial. Thymic weights increased (P < .01) with dose of pST in injected and implanted animals. Thymosin beta 4 increased (P < .05) in a pST dose-dependent manner in injected and implanted animals, but concentrations were increased more in implanted animals. Concentrations of thymosin beta 4 decreased or reached a plateau in gilts but continued to increase in barrows to the end of the trial. Thymosin alpha 1 concentrations were increased (P < .01) in barrows compared with gilts, but the concentrations were not related to dose of pST. Concentrations of pST in injected animals increased (P < .01) within 6 h after injection and had returned to basal concentrations by 24 h after injection. Concentrations of pST in implanted animals were dose-dependent (P < .05) and remained increased throughout the trial. Concentrations of IGF-I and -II were pST-dependent (P < .01) and increased throughout the trial period. Outside of the pST dose relationships, temporal changes in thymosin beta 4 were not highly related to changes in pST, IGF-I, or IGF-II. The pST dose-related increases in thymic weights and thymosin beta 4 concentrations are consistent with pST stimulation of the immune function in conjunction with overall increases of growth and efficiency of live weight gain in swine.

Topics: Animals; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Implants; Female; Growth Hormone; Injections, Intramuscular; Male; Obesity; Organ Size; Recombinant Proteins; Somatomedins; Swine; Swine Diseases; Thymosin; Thymus Gland