Sex-Dependent Attenuation of Plaque Growth After Treatment With Bone Marrow Mononuclear Cells
| Autor: | Harald C. Ott, Craig Stolen, Wendy Nelson, Xiangrong Xin, Angela Panoskaltsis-Mortari, Andrey G. Zenovich, Doris A. Taylor, Gabriel J. Caron, Samuel A. Barnes |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Apolipoprotein E medicine.medical_specialty Pathology Apolipoprotein B Physiology medicine.medical_treatment CD34 Coronary Artery Disease Granulocyte Peripheral blood mononuclear cell Mice Apolipoproteins E Internal medicine medicine Animals Progenitor cell Bone Marrow Transplantation Mice Knockout Sex Characteristics biology business.industry Mice Inbred C57BL medicine.anatomical_structure Endocrinology Cytokine Leukocytes Mononuclear biology.protein Female Bone marrow Cardiology and Cardiovascular Medicine business |
| Zdroj: | Circulation Research. 101:1319-1327 |
| ISSN: | 1524-4571 0009-7330 |
| Popis: | There are clinically relevant differences in symptomatology, risk stratification, and efficacy of therapies between men and women with coronary artery disease. Sex-based differences in plaque attenuation after administration of bone marrow mononuclear cells (BMNCs) are unknown. Forty-five male and 57 female apolipoprotein-E knockout (apoE −/− ) mice were fed a high-fat diet. At 14 weeks of age, animals received 4 biweekly intravenous sex-matched (males, n=11; females, n=13) or -mismatched (males, n=12; females, n=14) BMNCs obtained from C57BL6/J mice. The rest of the apoE −/− mice were vehicle treated (males, n=13; females, n=20) or were age-matched untreated controls (males, n=9; females, n=10). Aortic plaque burden, progenitor cell profiles in bone marrow (BM) and 22 circulating cytokines/chemokines were examined 1 week following the final injection. Only female BMNCs infused into male apoE −/− recipients significantly decreased plaque formation ( P + ( P =0.02), CD45 + ( P =0.0001), and AC133 + /CD34 + ( P =0.001) cell percentages in the BM of recipients but not with total serum cholesterol or percentage of BM-CD31 + /CD45 low cells. In a multivariate analysis, BM-AC133 + /CD34 + and BM-CD45 + percentage counts correlated with a lower plaque burden ( P r =−0.86, P =0.0004). In untreated apoE −/− mice of either sex, BM-AC133 + /CD34 + cells rose initially and then fell as plaque accumulated; however, BM-AC133 + /CD34 + percentages were higher in females at all times ( P ≤0.01). We have demonstrated an atheroprotective effect of female-derived BMNCs administered to male atherosclerotic apoE −/− mice; this reparative response correlated with the upregulation of BM-AC133 + /CD34 + and CD45 + cells and of circulating granulocyte colony-stimulating factor. Atherosclerotic female apoE −/− mice did not exhibit atheroprotection after BMNCs of either sex. Our findings may have implications for clinical cell therapy trials for coronary artery disease. Further exploration of sex-based differences in atheroprotection and vascular repair is warranted. |
| Databáze: | OpenAIRE |
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