transforming-growth-factor-alpha and Myocardial-Ischemia

Inflammation and genetics are both prominent mechanisms in the pathogenesis of atherosclerosis and arterial thrombosis. Accordingly, a number of population studies have explored the association of ischaemic heart disease with gene polymorphisms of the inflammatory molecules tumour necrosis factors (TNF) alpha and beta, transforming growth factors (TGF) beta1 and 2, interleukin (IL) 1 and its receptor antagonist (IL 1ra), CD14 (the receptor for lipopolysaccharide), P and E selectins, and platelet endothelial cell adhesion molecule (PECAM) 1. Although they are very preliminary and partly conflicting, the data provide some evidence that alterations in the genetics of the inflammatory system may modify the risk of ischaemic heart disease.

Topics: Adult; E-Selectin; Female; Humans; Inflammation; Interleukin-1; Lipopolysaccharide Receptors; Male; Middle Aged; Myocardial Ischemia; P-Selectin; Phenotype; Platelet Endothelial Cell Adhesion Molecule-1; Polymorphism, Genetic; Risk Factors; Transforming Growth Factor alpha; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Transforming growth factor-α (TGF-α) has been shown to augment mesenchymal stem cell-mediated cardioprotection during acute ischemia and reperfusion in isolated heart models. To determine whether this pretreatment strategy would be effective in vivo, we hypothesized that the intramyocardial injection of mesenchymal stem cells pretreated with TGF-α after coronary artery ligation would confer greater preservation of cardiac function, reduction in infarct size, and reduction myocardial inflammation.. Sprague-Dawley rats underwent left anterior descending coronary artery ligation. Ischemic border zones were injected 30 minutes later with vehicle (n = 11), 1 million mesenchymal stem cells (n = 9), or mesenchymal stem cells pretreated with TGF-α (250 ng/mL for 24 hours; n = 10). Cardiac function was assessed by echocardiography at 7 and 28 days after ligation. Infarct size was measured using triphenyltetrazolium chloride. Ischemic border zone cytokine expression was measured 30 days after infarction.. Myocardial function after ligation was greatest in hearts injected with cells pretreated with TGF-α in association with reduced ventricular remodeling and infarct size compared with vehicle-injected hearts. Myocardial interleukin 1β, interleukin 6, and TNF-α concentrations were lower, and Bcl-2 expression was higher, in hearts injected with either cell type. Vascular endothelial growth factor and matrix metalloproteinase-2 expression were highest in hearts that received pretreated cells.. Intramyocardial injection of mesenchymal stem cells pretreated with TGF-α further protects cardiac function and reduces infarct size compared with injection of untreated cells. Pretreating donor cells with TGF-α may be useful for enhancing cell-based therapies for myocardial ischemia.

Topics: Animals; Combined Modality Therapy; Male; Mesenchymal Stem Cell Transplantation; Myocardial Ischemia; Rats; Rats, Sprague-Dawley; Transforming Growth Factor alpha

Topics: Animals; Male; Mesenchymal Stem Cell Transplantation; Myocardial Ischemia; Transforming Growth Factor alpha