title: Angiotensin-converting enzyme inhibition induces apoptosis in erythroid precursors and affects insulin-like growth factor-1 in posttransplantation erythrocytosis.
abstract: A number of studies suggest that erythropoietin (Ep), angiotensin II, and insulin-like growth factor (IGF-1) are involved in the pathogenesis of posttransplantation erythrocytosis (PTE). Angiotensin-converting enzyme inhibitors (ACEI) are the treatment of choice in PTE, but their mechanism of action is unclear. It was shown previously that ACEI added directly to cultures of erythroid precursors from patients with PTE inhibit colony growth. In this report, the effect of ACEI on CD34+ erythroid precursor apoptosis was studied, as were hematocrit (Hct), Ep, IGF-1, and IGF-binding protein 3 (IGF-BP3) levels. Ten patients with PTE, 10 transplant control patients, and 7 normal control subjects were studied. Peripheral blood CD34+ cells were isolated, and apoptosis was assessed by annexin assay and DNA laddering before and during ACEI therapy. At the same time, Hct, Ep, IGF-1, and IGF-BP3 levels were measured. Baseline CD34+ cell number, CD34+ apoptosis, Ep, IGF-1, and IGF-BP3 levels were the same between PTE and transplant control subjects. ACEI therapy was associated with a striking increase in CD34+ cell apoptosis and a decrease in Hct in both groups. In contrast to control subjects, patients with PTE on ACEI showed a significant decrease in IGF-1 levels and a greater percentage decrease in Hct. In normal control subjects, ACEI therapy was associated with a fall in Hct but no change in CD34+ cell apoptosis. In PTE, ACEI-related increase in erythroid progenitor apoptosis may partially explain the ACEI-associated decrease in Hct. However, it is not clear that erythroid precursor apoptosis is related to changes in IGF-1 or IGF-BP3.
authors.affiliation: Department of Medicine, Montefiore Medical Center of the Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Daniel
authors.initials: D
authors.lastname: Glicklich
authors.affiliation: Department of Medicine, Montefiore Medical Center of the Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Larry
authors.initials: L
authors.lastname: Burris
authors.affiliation: Department of Pediatrics, Montefiore Medical Center of the Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Agnes
authors.initials: A
authors.lastname: Urban
authors.affiliation: Department of Surgery, Montefiore Medical Center of the Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Vivian
authors.initials: V
authors.lastname: Tellis
authors.affiliation: Department of Surgery, Montefiore Medical Center of the Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Stuart
authors.initials: S
authors.lastname: Greenstein
authors.affiliation: Department of Surgery, Montefiore Medical Center of the Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Richard
authors.initials: R
authors.lastname: Schechner
authors.affiliation: Department of Pediatrics, Montefiore Medical Center of the Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
authors.affiliation: Department of Medicine, Montefiore Medical Center of the Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Helena
authors.initials: H
authors.lastname: Croizat
mesh_terms: D000293:Adolescent; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D018952:Antigens, CD34 / Q000032:analysis; D017209:Apoptosis; D015672:Erythroid Precursor Cells / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D005260:Female; D017328:Fosinopril / Q000627:therapeutic use*; D006400:Hematocrit; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors*; D016030:Kidney Transplantation / Q000009:adverse effects*; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D011086:Polycythemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology*; D012016:Reference Values
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D018952:Antigens, CD34; D007334:Insulin-Like Growth Factor I; D017706:Lisinopril; D017328:Fosinopril