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<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
</div>
<div class="action-panel-control-wrap">
<label for="email-from" class="action-panel-label">
From:
</label>
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
</div>
<div class="action-panel-control-wrap">
<label for="email-citation-format" class="action-panel-label">
Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="l6Ck2gwttYzvCbse5s90cgDCX78aouA6CTmpF6ZP3zmZwCy4ILM2Go9gvbQmh58q">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="l6Ck2gwttYzvCbse5s90cgDCX78aouA6CTmpF6ZP3zmZwCy4ILM2Go9gvbQmh58q">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="l6Ck2gwttYzvCbse5s90cgDCX78aouA6CTmpF6ZP3zmZwCy4ILM2Go9gvbQmh58q">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="l6Ck2gwttYzvCbse5s90cgDCX78aouA6CTmpF6ZP3zmZwCy4ILM2Go9gvbQmh58q">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="l6Ck2gwttYzvCbse5s90cgDCX78aouA6CTmpF6ZP3zmZwCy4ILM2Go9gvbQmh58q">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="16601194">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https:///www.science.org/doi/10.1126/science.1124287?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub 0pubmed"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=4487&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=16601194&amp;db=pubmed&amp;nlmid=0404511"
title="See full text options at Atypon"
data-ga-category="full_text"
data-ga-action="Atypon"
data-ga-label="16601194"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.science.org-pb-assets-images-logos-pubmed-science.gif" alt="Atypon full text link"><span class="text">
Atypon
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/16601194/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=16601194&amp;db=pubmed&amp;nlmid=0404511"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="16601194"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/16601194/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/16601194/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="16601194" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F16601194%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="l6Ck2gwttYzvCbse5s90cgDCX78aouA6CTmpF6ZP3zmZwCy4ILM2Go9gvbQmh58q"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
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<p>
Aortic aneurysm and dissection are manifestations of Marfan syndrome (MFS), a disorder caused by mutations in the gene that encodes fibrillin-1. Selected manifestations of MFS reflect excessive signaling by the transforming growth factor-beta (TGF-beta) family of cytokines. We show that aortic aneurysm in a mouse model of MFS is associated with increased TGF-beta signaling and can be prevented by TGF-beta antagonists such as TGF-beta-neutralizing antibody or the angiotensin II type 1 receptor (AT1) blocker, losartan. AT1 antagonism also partially reversed noncardiovascular manifestations of MFS, including impaired alveolar septation. These data suggest that losartan, a drug already in clinical use for hypertension, merits investigation as a therapeutic strategy for patients with MFS and has the potential to prevent the major life-threatening manifestation of this disorder.
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<p> Fig. 1 </p>
</strong>
<div class="figure-caption-contents"><p> Postnatal treatment with TGF-β NAb.… </p></div>
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</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Fig. 1 </p>
</strong>
<div class="figure-caption-contents"><p> Postnatal treatment with TGF-β NAb. ( <b> A </b> to <b> H </b> ) Characterization of the… </p></div>
</div>
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Fig. 1
</strong>
<div class="figure-caption-contents">Postnatal treatment with TGF-β NAb. (<b>A</b> to <b>H</b>) Characterization of the ascending aorta in untreated wild-type mice [(A) and (E)] and <i>Fbn1</i><sup>C1039G/+</sup> mice treated with placebo [(B) and (F)], 1 mg/kg TGF-β NAb [(C) and (G)], and 10 mg/kg TGF-β NAb [(D) and (H)]. In (A) to (D), Verhoeff'svan Gieson (VVG) stain reveals diffuse disruption of elastic fiber architecture and thickening of the aortic media (delineated by arrows) in placebo-treated <i>Fbn1</i><sup>C1039G/+</sup> mice (B) relative to the normal elastic fiber architecture observed in wild-type mice (A). Improvement in both parameters is seen in NAb-treated <i>Fbn1</i><sup>C1039G/+</sup> mice [(C) and (D)]. Scale bars, 40 μm. In (E) to (H), immunohisto-chemistry (IH) reveals nuclear pSmad2, a marker for TGF-β signaling (arrows indicate representative positive nuclei). Increased pSmad2 is observed in the placebo-treated <i>Fbn1</i><sup>C1039G/+</sup> mice (F) relative to wild-type mice (E). Normalized pSmad2 staining is observed in the NAb-treated <i>Fbn1</i><sup>C1039G/+</sup> mice [(G) and (H)]. Scale bars, 50 μm. (<b>I</b>) Average aortic root growth (±SD) measured by echocardiogram over the 2-month treatment period. Note the reduced rate of growth in the NAb-treated mice relative to the placebo-treated <i>Fbn1</i><sup>C1039G/+</sup> mice. *<i>P</i> &lt; 0.0001, **<i>P</i> &lt; 0.03, †<i>P</i> = 0.11, ‡<i>P</i> = 1.0. (<b>J</b>) Average thickness (±SD) of the proximal ascending aortic media of four representative sections measured by an observer blinded to genotype and treatment arm. Note full normalization of thickness in NAb-treated <i>Fbn1</i><sup>C1039G/+</sup> mice. *<i>P</i> &lt; 0.01, †<i>P</i> = 0.91, ‡<i>P</i> = 0.38. (<b>K</b>) Average aortic wall architecture score (±SD) of the proximal ascending aorta. Three separate observers who were blinded to genotype and treatment arm graded elastic fiber architecture in four representative areas on a scale from 1 (completely intact elastic lamellae) to 4 (extensive fragmentation). Note the improvement in NAb-treated <i>Fbn1</i><sup>C1039G/+</sup> mice. *<i>P</i> &lt; 0.007, **<i>P</i> &lt; 0.0001, ***<i>P</i> &lt; 0.001, †<i>P</i> = 0.21.</div>
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<p> Fig. 2 </p>
</strong>
<div class="figure-caption-contents"><p> Prenatal treatment with losartan and… </p></div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Fig. 2 </p>
</strong>
<div class="figure-caption-contents"><p> Prenatal treatment with losartan and propranolol. ( <b> A </b> to <b> D </b> ) VVG staining… </p></div>
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Fig. 2
</strong>
<div class="figure-caption-contents">Prenatal treatment with losartan and propranolol. (<b>A</b> to <b>D</b>) VVG staining highlights intact elastic fiber architecture and normal ascending aortic wall thickness (arrows) in wild-type mice (A) and losartan-treated <i>Fbn1</i><sup>C1039G/+</sup> mice (D). Marked elastic fiber disruption and wall thickening is apparent in the placebo- and propranolol-treated <i>Fbn1</i><sup>C1039G/+</sup> mice [(B) and (C).] Scale bars, 40 μm. (<b>E</b>) Average aortic wall thickness (±SD) after 10 months of treatment. Note full normalization of wall thickness in losartan-treated <i>Fbn1</i><sup>C1039G/+</sup> mice relative to mice that received placebo or propranolol treatment. *<i>P</i> &lt; 0.0001, **<i>P</i> &lt; 0.002, †<i>P</i> = 0.24, ‡<i>P</i> = 0.19. (<b>F</b>) Average aortic wall architecture score (±SD) after treatment. Note the improvement in losartan-treated <i>Fbn1</i><sup>C1039G/+</sup> mice. *<i>P</i> &lt; 0.02, **<i>P</i> &lt; 0.0001, †<i>P</i> = 0.16.</div>
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<strong class="figure-label">
<p> Fig. 3 </p>
</strong>
<div class="figure-caption-contents"><p> Postnatal treatment with losartan and… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Fig. 3 </p>
</strong>
<div class="figure-caption-contents"><p> Postnatal treatment with losartan and propranolol. ( <b> A </b> to <b> H </b> ) VVG staining… </p></div>
</div>
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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Fig. 3
</strong>
<div class="figure-caption-contents">Postnatal treatment with losartan and propranolol. (<b>A</b> to <b>H</b>) VVG staining [(A) to (D)] and pSmad2 immunostaining [(E) to (H)] of aortic wall. Elastic lamellae are intact and aortic media is of normal thickness in the wild-type (A) and losartan-treated <i>Fbn1</i><sup>C1039G/+</sup> mice (D). Placebo-and propranolol-treated <i>Fbn1</i> <sup>C1039G/+</sup> mice [(B) and (C)] have diffuse fragmentation of elastic fibers and thickening of the aortic media (arrows). Scale bars, 50 μm. Nuclear pSmad2 staining is decreased in the aortic media of wild-type (E) and losartan-treated <i>Fbn1</i><sup>C1039G/+</sup> mice (H). Marked increase in nuclear staining for pSmad2 (representative positive cells denoted by arrowheads) is seen in the <i>Fbn1</i><sup>C1039G/+</sup> mice treated with placebo (F) and propranolol (G). Scale bars, 40 μm. (<b>I</b>) Average aortic root growth (±SD) during the 6 months of treatment. Note that aortic root growth in <i>Fbn1</i><sup>C1039G/+</sup> mice treated with propranolol is less than that with placebo, yet remains greater than that seen in wild-type mice. Losartan treatment normalizes growth rate. *<i>P</i> &lt; 0.0001, **<i>P</i> &lt; 0.001, ***P &lt; 0.02, †<i>P</i> = 0.55. (<b>J</b>) Average aortic wall thickness (±SD). Aortic wall thickness in losartan-treated <i>Fbn1</i><sup>C1039G/+</sup> mice is reduced relative to placebo- and propranolol-treated mice and is indistinguishable from that seen in wild-type mice. *<i>P</i> &lt; 0.002, **<i>P</i> &lt; 0.0001, ***<i>P</i> &lt; 0.05, †<i>P</i> = 0.67, ‡<i>P</i> = 0.17. (<b>K</b>) Average aortic wall architecture (±SD). Note full normalization achieved with losartan treatment. *<i>P</i> &lt; 0.002, **<i>P</i> &lt; 0.0001, ***<i>P</i> &lt; 0.05, †<i>P</i> = 0.20, ‡<i>P</i> = 0.47.</div>
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aria-describedby="figure-caption-3"
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data-pmc-id="PMC1482474"
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<img class="figure-thumb" itemprop="thumbnail"
id="article-image-3"
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<p> Fig. 4 </p>
</strong>
<div class="figure-caption-contents"><p> Postnatal losartan treatment of lung… </p></div>
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<strong class="figure-label">
<p> Fig. 4 </p>
</strong>
<div class="figure-caption-contents"><p> Postnatal losartan treatment of lung disease in <i> Fbn1 </i> <sup> C1039G/+ </sup> mice. Histologic analysis of… </p></div>
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Fig. 4
</strong>
<div class="figure-caption-contents">Postnatal losartan treatment of lung disease in <i>Fbn1</i><sup>C1039G/+</sup> mice. Histologic analysis of lung in wild-type mice (<b>A</b>) shows normal airspace caliber. <i>Fbn1</i><sup>C1039G/+</sup> mice treated with placebo (<b>B</b>) show diffuse distal airspace widening (example delineated with arrows). Distal airspace caliber is reduced in <i>Fbn1</i><sup>C1039G/+</sup> mice treated with losartan (<b>C</b>). Scale bars, 500 μm. (<b>D</b>) Average mean linear intercept, a marker of airspace caliber, is greater for placebo-treated <i>Fbn1</i><sup>C1039G/+</sup> mice than for untreated wild-type and losartan-treated <i>Fbn1</i><sup>C1039G/+</sup> mice. *<i>P</i> &lt; 0.01, **<i>P</i> &lt; 0.001.</div>
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