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      Gender Differences in Postinfarction Left Ventricular Remodeling

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          Abstract

          Objective: Previous studies suggest that gender affects the adaptive responses of the heart to some forms of cardiac overload. It is unknown whether gender influences left ventricular (LV) remodeling after myocardial infarction (MI). Methods: We performed transthoracic echocardiographic-Doppler examinations in age-matched male (n = 17) and female (n = 16) rats before, and 1 and 6 weeks after transmural MI or sham surgery. Results: Following large MI (male = 45 ± 1% LV circumference vs. female = 48 ± 4%, p = NS), both male and female rats developed progressive LV dilatation. Infarctions caused a similar degree of global and regional LV systolic dysfunction in males and females. Male rats had significant increases in the thickness of the noninfarcted posterior wall by 6 weeks after MI. However, posterior wall thickness did not change in the infarcted female rats. Average myocyte diameter in the noninfarcted region of the heart was also greater in male than female MI rats. The combination of increased cavity size with little change in wall thickness resulted in a greater decline in relative wall thickness in the female rats compared to the males. Male rats with MI showed progressively restricted LV diastolic filling as assessed by transmitral Doppler recordings. Female rats had less of an increase in the ratio of early to late transmitral velocities and less of an increase in the E wave deceleration rate after MI. Conclusions: Female rats showed a different pattern of LV remodeling than males with less of an increase in thickness of the noninfarcted portions of the left ventricle than males, but comparable LV cavity enlargement and systolic dysfunction. Despite similar infarct size, females developed less pronounced abnormalities of LV diastolic filling. We hypothesize that the gender-related differences in postinfarction LV remodeling may contribute to the different LV filling patterns, and might ultimately relate to differences in clinical outcome.

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          ISIS-4: A randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58 050 patients with suspected acute myocardial infarction

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            Gender-specific differences in expression of mRNAs for functional and structural proteins in rat ventricular myocardium.

            Sex-related differences in predisposition to heart diseases have long been recognized. The molecular and cellular bases for this difference are unknown. In this study we have compared expression of genes for various structural and functional proteins of muscle and interstitial compartments of the myocardium in the adult and neonatal, male and female rat heart. We have also compared cultured cardiac fibroblasts from male and female hearts with regards to gene expression and proliferative capacity. We showed that in the adult rats, the abundance of mRNAs for contractile proteins alpha- and beta-myosin heavy chain (MHC) is higher in the heart of female rats than in that of age-matched male rats. However, the difference in mRNA level for alpha-MHC was more drastic (736%, P < 0.001) than that for beta-MHC (469%, P < 0.001). mRNA levels for sarcomeric actin in the female heart were greater by 79% (P < 0.001). Collagen type I had a significantly higher (303%, P < 0.01) mRNA level in the female heart compared with the male heart. mRNAs for TGF-beta 1, cytoskeletal actin and connexin 43 were also higher (150%, P < 0.01; 130%, P < 0.01, and 150%, P < 0.01, respectively) in the female heart compared with age-matched male heart. There were no significant sex-related differences at the mRNA levels for the above proteins in ventricular tissue from neonatal male and female littermates. At the cellular level, cardiac fibroblasts obtained from adult and neonatal hearts of both sexes were comparable with respect to the abundance of mRNAs for collagen type I, TGF-beta 1 or cytoskeletal actin. However, DNA synthesis, as measured by [3H]thymidine incorporation, was higher (328%, P < 0.01) in cells from adult female heart compared with that in cells from adult male rat heart. This difference was even more pronounced in cardiac fibroblasts obtained from newborn female rats (933%, P < 0.001) compared with that in cells obtained from newborn male rat hearts. Together, these findings show that there are sex-related differences in gene expression for most major proteins in heart tissue and that this phenomenon is associated with the post-pubertal period. These findings further suggest that sex-related differential gene expression and DNA synthesis in cardiac cells are due to the regulatory effects of male- and female-specific hormones.
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              Author and article information

              Journal
              CRD
              Cardiology
              10.1159/issn.0008-6312
              Cardiology
              S. Karger AG
              0008-6312
              1421-9751
              1999
              September 1999
              24 September 1999
              : 91
              : 3
              : 173-183
              Affiliations
              aCardiovascular Division, Salt Lake City Veterans Affairs Medical Center and University of Utah, and cDepartment of Pathology, University of Utah, Salt Lake City, Utah, and bCharlesA. Dana Research Institute and Harvard-Thorndike Laboratory, Beth Israel-Deaconess Medical Center (Cardiovascular Division), Harvard Medical School, Boston, Mass., USA
              Article
              6906 Cardiology 1999;91:173–183
              10.1159/000006906
              10516411
              © 1999 S. Karger AG, Basel

              Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

              Page count
              Figures: 4, Tables: 4, References: 48, Pages: 11
              Categories
              General Cardiology, Basic Science

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