<table><tbody><tr><td><table cellpadding="2" cellspacing="0" width="600"><tbody><tr bgcolor="#cccccc" valign="top"><td colspan="2"><table width="600"><tbody><tr><td><strong class="acc" id="GSE267813"><a href="/geo/query/acc.cgi?acc=GSE267813" onmouseout="onLinkOut('HelpMessage' , geo_empty_help)" onmouseover="onLinkOver('HelpMessage' , geoaxema_recenter)">Series GSE267813</a></strong></td>

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<td align="right" onmouseout="onLinkOut('HelpMessage' , geo_empty_help)" onmouseover="onLinkOver('HelpMessage' , geoaxema_gds)"><a href="/gds/?term=GSE267813[Accession]">Query DataSets for GSE267813</a></td>

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<tr valign="top"><td>Status</td>

<td>Public on May 24, 2024</td>

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<tr valign="top"><td nowrap="">Title</td>

<td style="text-align: justify">A KLF2-BMPER-Smad1/5 checkpoint regulates high fluid shear stress-mediated artery remodeling</td>

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<tr valign="top"><td nowrap="">Organism</td>

<td><a href="/Taxonomy/Browser/wwwtax.cgi?mode=Info&amp;id=9606" onmouseout="onLinkOut('HelpMessage' , geo_empty_help)" onmouseover="onLinkOver('HelpMessage' , geoaxema_organismus)">Homo sapiens</a></td>

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<tr valign="top"><td nowrap="">Experiment type</td>

<td>Expression profiling by high throughput sequencing<br></td>

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<tr valign="top"><td nowrap="">Summary</td>

<td style="text-align: justify">Vascular remodeling to match arterial diameter to tissue metabolic requirements commonly fails in ischemic disease. Endothelial cells (EC) sense fluid shear stress (FSS) from blood flow to maintain FSS within a narrow range in healthy vessels. Higher FSS induces vessel outward remodeling to return FSS to physiological levels, but mechanisms are poorly understood. We previously reported that Smad1/5 is maximally activated at physiological FSS and suppressed at higher flow. The Smad1/5 pathway opposes activation of Akt, suggesting that inhibiting Smad1/5 may be required for outward remodeling. Here, we report that suppression of Smad1/5 at high FSS is mediated by elevated KLF2, which induces the BMP pathway inhibitor BMPER, which suppresses Smad1/5 and de-inhibits Akt. In a mouse arteriovenous fistula (AVF) model, high FSS induces arterial outward remodeling coincident with elevated BMPER expression and Smad1/5 inactivation. Endothelial BMPER deletion impaired blood flow recovery and vascular remodeling in the AVF and a hindlimb ischemia (HLI) model, with the latter reversed by BMP9/10 blocking antibodies (bAbs). In both STZ-induced type 1 and HFD-induced type 2 diabetic mice that show poor recovery from HLI, BMP9/10 bAbs improved outcomes. Thus, suppression of Smad1/5 is required for high FSS-mediated outward remodeling and is a potential therapeutic approach for ischemic disease.<br></td>

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<tr valign="top"><td nowrap="">&nbsp;</td>

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<tr valign="top"><td nowrap="">Overall design</td>

<td style="text-align: justify">Human umbilical vein endothelial cells (HUVECs) were transfected with Ctrl (siCtrl) or KLF2 (siKLF2) siRNA for 4 days, total RNA was extracted and subjected to RNAseq, n=4 samples for each group.<br></td>

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<tr valign="top"><td nowrap="">&nbsp;</td>

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<tr valign="top"><td>Contributor(s)</td>

<td><a href="/pubmed/?term=Deng H[Author]">Deng H</a></td>

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<tr valign="top"><td nowrap="">Citation(s)</td>

<td><span class="pubmed_id" id="39196179"><!--?xml version="1.0" encoding="UTF-8"?-->

<div class="PubmedCitation"><ul><li><span class="authors">Deng H, Zhang J, Wang Y, Joshi D et al. </span><span class="title">A KLF2-BMPER-Smad1/5 checkpoint regulates high fluid shear stress-mediated artery remodeling. </span><span class="source">Nat Cardiovasc Res</span> 2024 Jul;3(7):785-798. PMID:&nbsp;<a title="Link to PubMed record" href="https://www.ncbi.nlm.nih.gov/pubmed/39196179">39196179</a></li></ul></div>

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<tr valign="top"><td colspan="2"><span id="geo2r"><button class="button" id="geo2r_button"><span class="">Analyze with GEO2R</span></button></span> <span id="rnaseq_counts"><button class="button" id="download_button"><span class="">Download RNA-seq counts</span></button></span></td></tr>

<tr bgcolor="#eeeeee" valign="top"><td>Submission date</td>

<td>May 18, 2024</td>

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<tr bgcolor="#eeeeee" valign="top"><td>Last update date</td>

<td>Aug 29, 2024</td>

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<tr bgcolor="#eeeeee" valign="top"><td>Contact name</td>

<td>Hanqiang Deng</td>

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<tr bgcolor="#eeeeee" valign="top"><td nowrap="">E-mail(s)</td>

<td><a href="mailto:hanqiang.deng@yale.edu">hanqiang.deng@yale.edu</a><br></td>

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<tr bgcolor="#eeeeee" valign="top"><td nowrap="">Phone</td>

<td style="text-align: justify">475 414 9546<br></td>

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<tr bgcolor="#eeeeee" valign="top"><td nowrap="">Organization name</td>

<td style="text-align: justify">Yale University<br></td>

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<tr bgcolor="#eeeeee" valign="top"><td nowrap="">Department</td>

<td style="text-align: justify">Yale Cardiovascular Research Center<br></td>

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<tr bgcolor="#eeeeee" valign="top"><td nowrap="">Street address</td>

<td style="text-align: justify">116 Court Street<br></td>

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<tr bgcolor="#eeeeee" valign="top"><td nowrap="">City</td>

<td style="text-align: justify">New Haven</td>

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<tr bgcolor="#eeeeee" valign="top"><td nowrap="">State/province</td>

<td style="text-align: justify">CT</td>

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<tr bgcolor="#eeeeee" valign="top"><td nowrap="">ZIP/Postal code</td>

<td style="text-align: justify">06511</td>

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<tr bgcolor="#eeeeee" valign="top"><td nowrap="">Country</td>

<td style="text-align: justify">USA</td>

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<tr valign="top"><td nowrap="">&nbsp;</td>

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