Sex-related resistance to myocardial ischemia-reperfusion injury is associated with high constitutive ARC expression
| Autor: | Wobbe Bouma, Bradley G. Leshnower, Robin Hinmon, rd Joseph H. Gorman, Mio Noma, Shinya Kanemoto, Muneaki Matsubara, Robert C. Gorman |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Physiology medicine.drug_class Ovariectomy Blotting Western Ischemia Myocardial Infarction Hemodynamics Apoptosis Myocardial Reperfusion Injury Cell Separation Biology Body Temperature Electrocardiography Physiology (medical) Internal medicine medicine Animals Myocytes Cardiac Myocardial infarction Ultrasonography bcl-2-Associated X Protein Sex Characteristics Arc (protein) Estradiol Estrogens Articles medicine.disease CARD Signaling Adaptor Proteins Endocrinology Proto-Oncogene Proteins c-bcl-2 Estrogen Circulatory system Female Rabbits Blood Gas Analysis Cardiology and Cardiovascular Medicine Reperfusion injury Sex characteristics |
| Popis: | The female sex has been associated with improved myocardial salvage after ischemia and reperfusion (I/R). Estrogen, specifically 17β-estradiol, has been demonstrated to mediate this phenomenon by limiting cardiomyocyte apoptosis. We sought to quantitatively assess the effect of sex, ovarian hormone loss, and I/R on myocardial Bax, Bcl-2, and apoptosis repressor with caspase recruitment domain (ARC) expression. Male ( n = 48), female ( n = 26), and oophorectomized female ( n = 20) rabbits underwent 30 min of regional ischemia and 3 h of reperfusion. The myocardial area at risk and infarct size were determined using a double-staining technique and planimetry. In situ oligo ligation was used to assess apoptotic cell death. Western blot analysis was used to determine proapoptotic (Bax) and antiapoptotic (Bcl-2 and ARC) protein levels in all three ischemic groups and, additionally, in three nonischemic groups. Infarct size (43.7 ± 3.2%) and apoptotic cell death (0.51 ± 0.10%) were significantly attenuated in females compared with males (56.4 ± 1.6%, P < 0.01, and 4.29 ± 0.95%, P < 0.01) and oophorectomized females (55.7 ± 3.4%, P < 0.05, and 4.36 ± 0.51%, P < 0.01). Females expressed significantly higher baseline ARC levels (3.62 ± 0.29) compared with males (1.78 ± 0.18, P < 0.01) and oophorectomized females (1.08 ± 0.26, P < 0.01). Males expressed a significantly higher baseline Bax-to-Bcl-2 ratio (4.32 ± 0.99) compared with females (0.65 ± 0.13, P < 0.01) and oophorectomized females (0.42 ± 0.10, P < 0.01). I/R significantly reduced Bax-to-Bcl-2 ratios in males. In all other groups, ARC levels and Bax-to-Bcl-2 ratios did not significantly change. These results support the conclusion that in females, endogenous estrogen limits I/R-induced cardiomyocyte apoptosis by producing a baseline antiapoptotic profile, which is associated with estrogen-dependent high constitutive myocardial ARC expression. |
| Databáze: | OpenAIRE |
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