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<title>Loss of Caveolin-1 Induces an Invasive, Pro-Proliferative, and Pro-Inflammatory Phenotype in Human Pulmonary Artery Endothelial Cells | NIH Research Festival</title>
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<article><div class="banner banner--gray banner--compact" style="--banner-background-image: url('/sites/default/files/media/image/2021-03/2015.jpg');--banner-background-focus: 50% 50%"><div class="banner__wrapper"><div class="banner__container"><h2 class="banner__heading">NIH Research Festival</h2><div class="banner__content"><p><strong><time datetime="2015-09-16">September 16</time> – <time datetime="2015-09-18">18, 2015</time></strong></p></div></div></div></div></article>
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<div class="section"><div data-drupal-messages-fallback class="hidden"></div></div><main role="main"><div id="main-content" tabindex="-1"></div><div class="section"><div class="content-sidebar"><div class="content-sidebar__main"><div class="content-sidebar__main-content"><div id="block-mainpagecontent-2"><article><h1>Loss of Caveolin-1 Induces an Invasive, Pro-Proliferative, and Pro-Inflammatory Phenotype in Human Pulmonary Artery Endothelial Cells</h1><div class="schedule"><div class="schedule__label"><div class="schedule__label-text"><time datetime="2015-09-17">Thursday, September 17, 2015</time>
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– Poster Session III
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</div></div><div class="schedule__content"><div class="schedule__item"><div class="schedule__time">3:30 – 5:00 p.m.</div><div class="schedule__description"><p><strong>FAES Terrace</strong></p></div><div class="schedule__description"><p><strong>CC</strong></p></div><div class="schedule__description"><p><strong>CELLBIO-8</strong></p></div></div></div></div><h2>Authors</h2><ul><li>S Gairhe</li><li>KS Awad</li><li>JM Elinoff</li><li>RL Danner</li></ul><h2>Abstract</h2><p>Pulmonary arterial hypertension (PAH) is a rare disease characterized by a pro-proliferative endothelial cell phenotype, vascular inflammation and pulmonary vessel remodeling culminating in right ventricular failure and ultimately death. With the advent of selective pulmonary vasodilator therapy, outcomes for PAH patients have improved, but mortality still remains unacceptably high. Caveolin-1 (CAV1) is an endothelial scaffolding protein located in flask-shaped invaginations present in the plasma membrane. Recently, a heterozygous single nucleotide deletion resulting in CAV1 loss-of-function has been linked to the development of PAH. However, the relationship between CAV1 loss-of-function and the dysfunctional pulmonary vascular phenotype in PAH is unknown. Here, we hypothesized that CAV1 loss-of-function in the pulmonary artery endothelium leads to a hyperproliferative, pro-inflammatory phenotype that contributes to the pathogenic pulmonary vascular remodeling seen in patients with PAH. In primary, human pulmonary artery endothelial cells (PAECs), CAV1 was knocked down using siRNA approach. This produced an efficient ≥80% knockdown of CAV1. Cells were then examined for proliferation, migration and the expression of inflammatory mediators and markers. Using an MTS assay and ATP production, we found increased cell proliferation in siCAV1 compared to siControl treated cells. Loss of CAV1 function in PAECs also increased their ability to migrate. Similarly, the mRNA and protein expression of IL-6, ICAM1 and VCAM1 was increased after loss of CAV1. These findings demonstrate that CAV1 loss-of-function in PAECs leads to a dysfunctional pro-proliferative and pro-inflammatory phenotype. Thus, CAV1 gene silencing may be a useful in vitro model to study molecular mechanisms important to PAH pathogenesis.</p><p><strong>Scientific Focus Area</strong>: Cell Biology</p><p class="updated"><small>This page was last updated on Friday, March 26, 2021</small></p></article>
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