![](http://investorshub.advfn.com/images/default_ih_profile2_4848.jpg?cb=0)
Tuesday, November 06, 2012 2:52:00 PM
Session: AOS.703.02a-Novel Signaling Pathways in the Regulation of Endothelial Function
Presentation: 13186 - Development of Novel, Mechanism-Based Therapies to Prevent the Cardiovascular Complications of the Antiphospholipid Syndrome
Pres Time: Wednesday, Nov 07, 2012, 10:00 AM -10:15 AM
Location: Hall A-8
Pres. Time: Wednesday, Nov 07, 2012, 10:00 AM -10:15 AM
Specialty: +703. Endothelium, Vascular Tone and Nitric Oxide
Keywords: Endothelial function; Nitric oxide; Cardiovascular therapeutics; Thrombosis; Angiogenesis
Authors: Victoria Ulrich, Philip Shaul, Philip Thorpe, Chieko Mineo, UT Southwestern, Dallas, TX
Abstract: Patients with antiphospholipid syndrome (APS) have circulating antiphospholipid antibodies (aPL) and increased risk of thrombosis as well as non-thrombotic vascular disease. Current APS treatment is limited to anticoagulation, which targets only a portion of APS-related disease and has modest efficacy and serious potential complications. We previously showed that aPL antagonism of endothelial NO synthase (eNOS) underlies APS-associated thrombosis. Seeking to develop therapies directed at the initiating processes for both APS-related thrombosis and non-thrombotic vascular disease, we studied the basis for eNOS antagonism by aPL and also determined how aPL impact endothelial repair. In scratch assays with bovine aortic endothelial cells (BAEC), we found that in contrast to IgG from normal healthy subjects (NHIgG) which had no effect, polyclonal aPL from APS patients inhibited migration stimulated by VEGF. The migratory response was restored by the NO donor S-nitroso-N-acetylpenicillamine, a monoclonal antibody (mAb) to the cell surface protein ß2GPI had effects identical to aPL, and aPL antagonism of migration was prevented by siRNA knockdown of apolipoprotein E receptor 2 (apoER2). Thus, the ß2GPI/apoER2-mediated eNOS antagonism that we previously discovered underlies aPL-induced thrombosis also antagonizes endothelial cell migration. Mimicking the cell culture findings, in C57BL/6 male mice carotid artery reendothelialization was attenuated by aPL treatment, and this was fully prevented by the NO donor molsidomine. We then screened a series of mAb to ß2GPI in assays of eNOS activation in BAEC. Whereas many mirrored aPL and antagonized eNOS, one anti-ß2GPI mAb designated 1N11 had no effect when tested alone and it fully prevented aPL action. 1N11 also prevented aPL inhibition of endothelial cell migration, and it rescued normal carotid artery reendothelialization in aPL-treated mice. Thus, by bypassing or disrupting how aPL antagonize eNOS, an NO donor or a select mAb to ß2GPI can afford protection from the endothelial actions of aPL that underlie the vascular manifestations of APS. Such mechanism-based therapies offer the promise of greater efficacy and fewer complications in patients with this often life-threatening disorder.
Disclosures: V. Ulrich, None; P. Shaul, None; P. Thorpe, Peregrine Pharmaceuticals, Inc., Significant,Other Research Support; Peregrine Pharmaceuticals, Inc., Significant,Ownership Interest; Peregrine Pharmaceuticals, Inc., Significant,Consultant/Advisory Board; C. Mineo, None.
Note that 1N11 = PGN635 the fully human version of bavi
Recent CDMO News
- Avid Bioservices Earns Committed Badge from EcoVadis for Sustainability Performance • GlobeNewswire Inc. • 05/23/2024 12:05:46 PM
- Avid Bioservices to Participate at Upcoming Investor Conferences • GlobeNewswire Inc. • 05/07/2024 08:05:11 PM
- Avid Bioservices Reports Financial Results for Third Quarter Ended January 31, 2024 • GlobeNewswire Inc. • 04/24/2024 09:25:33 PM
- Avid Bioservices Announces Receipt of Deficiency Notice from Nasdaq Regarding Late Form 10-Q • GlobeNewswire Inc. • 03/20/2024 11:00:10 AM
- Form 8-K - Current report • Edgar (US Regulatory) • 03/07/2024 11:30:11 AM
- Avid Bioservices Announces Pricing of Private Placement of Convertible Notes • GlobeNewswire Inc. • 03/07/2024 04:58:48 AM
- Avid Bioservices Announces Proposed Private Placement of Convertible Notes • GlobeNewswire Inc. • 03/06/2024 09:32:07 PM
- Avid Bioservices Announces Certain Preliminary Financial Results for Third Quarter Ended January 31, 2024 • GlobeNewswire Inc. • 03/06/2024 09:31:28 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 03/06/2024 09:30:18 PM
- Form SC 13G/A - Statement of acquisition of beneficial ownership by individuals: [Amend] • Edgar (US Regulatory) • 01/26/2024 09:57:52 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 01/13/2024 12:34:35 AM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 01/12/2024 12:39:18 AM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 01/12/2024 12:38:30 AM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 01/12/2024 12:37:38 AM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 01/12/2024 12:36:27 AM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 01/12/2024 12:35:47 AM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 01/11/2024 12:56:02 AM
- Form SC 13G/A - Statement of acquisition of beneficial ownership by individuals: [Amend] • Edgar (US Regulatory) • 01/08/2024 09:32:36 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 01/04/2024 12:56:18 AM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 01/04/2024 12:55:07 AM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 01/04/2024 12:53:58 AM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 01/04/2024 12:51:57 AM
- Form SC 13G - Statement of acquisition of beneficial ownership by individuals • Edgar (US Regulatory) • 12/19/2023 09:05:52 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 12/19/2023 12:34:08 AM
VAYK Exited Caribbean Investments for $320,000 Profit • VAYK • Jun 27, 2024 9:00 AM
North Bay Resources Announces Successful Flotation Cell Test at Bishop Gold Mill, Inyo County, California • NBRI • Jun 27, 2024 9:00 AM
Branded Legacy, Inc. and Hemp Emu Announce Strategic Partnership to Enhance CBD Product Manufacturing • BLEG • Jun 27, 2024 8:30 AM
POET Wins "Best Optical AI Solution" in 2024 AI Breakthrough Awards Program • POET • Jun 26, 2024 10:09 AM
HealthLynked Promotes Bill Crupi to Chief Operating Officer • HLYK • Jun 26, 2024 8:00 AM
Bantec's Howco Short Term Department of Defense Contract Wins Will Exceed $1,100,000 for the current Quarter • BANT • Jun 25, 2024 10:00 AM