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Alan daugherty

Mary B Sheppard, Alan Daugherty, Hong Lu
No abstract text is available yet for this article.
August 2016: Journal of Thoracic Disease
Hong Lu, Mary Sheppard, Alan Daugherty
No abstract text is available yet for this article.
October 2016: Current Opinion in Lipidology
Hong Lu, Deborah A Howatt, Anju Balakrishnan, Mark J Graham, Adam E Mullick, Alan Daugherty
OBJECTIVE: Gain-of-function mutations of PCSK9 (proprotein convertase subtilisin/kexin type 9) lead to hypercholesterolemia. This study was to determine whether infection of normocholesterolemic mice with an adeno-associated viral (AAV) vector expressing a gain-of-function mutation of mouse PCSK9 increased angiotensin II (AngII)-induced abdominal aortic aneurysms. APPROACH AND RESULTS: In an initial study, male C57BL/6 mice were injected intraperitoneally with either an empty vector or PCSK9 gain-of-function mutation (D377Y)...
September 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Mary Sheppard, Debra L Rateri, Alan Daugherty
No abstract text is available yet for this article.
June 28, 2016: Journal of the American College of Cardiology
Alan Daugherty, Robert A Hegele, Nigel Mackman, Daniel J Rader, Ann Marie Schmidt, Christian Weber
No abstract text is available yet for this article.
July 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Xiaofeng Chen, Debra L Rateri, Deborah A Howatt, Anju Balakrishnan, Jessica J Moorleghen, Lisa A Cassis, Alan Daugherty
AngII and TGF-β interact in development of thoracic and abdominal aortic diseases, although there are many facets of this interaction that have not been clearly defined. The aim of the present study was to determine the effects of TGF-β neutralization on AngII induced-aortic pathologies. Male C57BL/6J mice were administered with either a rabbit or mouse TGF-β neutralizing antibody and then infused with AngII. The rabbit TGF-β antibody modestly reduced serum TGF-β concentrations, with no significant enhancements to AngII-induced aneurysm or rupture...
2016: PloS One
Ilenia Simeoni, Jonathan C Stephens, Fengyuan Hu, Sri V V Deevi, Karyn Megy, Tadbir K Bariana, Claire Lentaigne, Sol Schulman, Suthesh Sivapalaratnam, Minka J A Vries, Sarah K Westbury, Daniel Greene, Sofia Papadia, Marie-Christine Alessi, Antony P Attwood, Matthias Ballmaier, Gareth Baynam, Emilse Bermejo, Marta Bertoli, Paul F Bray, Loredana Bury, Marco Cattaneo, Peter Collins, Louise C Daugherty, Rémi Favier, Deborah L French, Bruce Furie, Michael Gattens, Manuela Germeshausen, Cedric Ghevaert, Anne C Goodeve, Jose A Guerrero, Daniel J Hampshire, Daniel P Hart, Johan W M Heemskerk, Yvonne M C Henskens, Marian Hill, Nancy Hogg, Jennifer D Jolley, Walter H Kahr, Anne M Kelly, Ron Kerr, Myrto Kostadima, Shinji Kunishima, Michele P Lambert, Ri Liesner, José A López, Rutendo P Mapeta, Mary Mathias, Carolyn M Millar, Amit Nathwani, Marguerite Neerman-Arbez, Alan T Nurden, Paquita Nurden, Maha Othman, Kathelijne Peerlinck, David J Perry, Pawan Poudel, Pieter Reitsma, Matthew T Rondina, Peter A Smethurst, William Stevenson, Artur Szkotak, Salih Tuna, Christel van Geet, Deborah Whitehorn, David A Wilcox, Bin Zhang, Shoshana Revel-Vilk, Paolo Gresele, Daniel B Bellissimo, Christopher J Penkett, Michael A Laffan, Andrew D Mumford, Augusto Rendon, Keith Gomez, Kathleen Freson, Willem H Ouwehand, Ernest Turro
Inherited bleeding, thrombotic, and platelet disorders (BPDs) are diseases that affect ∼300 individuals per million births. With the exception of hemophilia and von Willebrand disease patients, a molecular analysis for patients with a BPD is often unavailable. Many specialized tests are usually required to reach a putative diagnosis and they are typically performed in a step-wise manner to control costs. This approach causes delays and a conclusive molecular diagnosis is often never reached, which can compromise treatment and impede rapid identification of affected relatives...
June 9, 2016: Blood
Xiaofeng Chen, Deborah A Howatt, Anju Balakrishnan, Jessica J Moorleghen, Congqing Wu, Lisa A Cassis, Alan Daugherty, Hong Lu
OBJECTIVE: Angiotensin-converting enzyme (ACE) is present in many cell types of atherosclerotic lesions. This study determined whether ACE activity in endothelial and smooth muscle cells (SMCs), 2 major resident cell types of the aorta, contributes to hypercholesterolemia-induced atherosclerosis. APPROACH AND RESULTS: All study mice were in low-density lipoprotein receptor(-/-) background. To determine the contribution of ACE on endothelial cells to atherosclerosis, female ACE floxed mice were bred to male Tie2-Cre transgenic mice...
June 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Hong Lu, Lisa A Cassis, Craig W Vander Kooi, Alan Daugherty
Angiotensinogen (AGT) is the sole precursor of all angiotensin peptides. Although AGT is generally considered as a passive substrate of the renin-angiotensin system, there is accumulating evidence that the regulation and functions of AGT are intricate. Understanding the diversity of AGT properties has been enhanced by protein structural analysis and animal studies. In addition to whole-body genetic deletion, AGT can be regulated in vivo by cell-specific procedures, adeno-associated viral approaches and antisense oligonucleotides...
July 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Cong-Lin Liu, Holger Wemmelund, Yi Wang, Mengyang Liao, Jes S Lindholt, Søren P Johnsen, Henrik Vestergaard, Cleverson Fernandes, Galina K Sukhova, Xiang Cheng, Jin-Ying Zhang, Chongzhe Yang, Xiaozhu Huang, Alan Daugherty, Bruce D Levy, Peter Libby, Guo-Ping Shi
OBJECTIVE: Both asthma and abdominal aortic aneurysms (AAA) involve inflammation. It remains unknown whether these diseases interact. APPROACH AND RESULTS: Databases analyzed included Danish National Registry of Patients, a population-based nationwide case-control study included all patients with ruptured AAA and age- and sex-matched AAA controls without rupture in Denmark from 1996 to 2012; Viborg vascular trial, subgroup study of participants from the population-based randomized Viborg vascular screening trial...
March 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Hong Lu, Congqing Wu, Deborah A Howatt, Anju Balakrishnan, Jessica J Moorleghen, Xiaofeng Chen, Mingming Zhao, Mark J Graham, Adam E Mullick, Rosanne M Crooke, David L Feldman, Lisa A Cassis, Craig W Vander Kooi, Alan Daugherty
OBJECTIVE: This study determined whether angiotensinogen (AGT) has angiotensin II-independent effects using multiple genetic and pharmacological manipulations. APPROACH AND RESULTS: All study mice were in low-density lipoprotein receptor -/- background and fed a saturated fat-enriched diet. In mice with floxed alleles and a neomycin cassette in intron 2 of the AGT gene (hypoAGT mice), plasma AGT concentrations were >90% lower compared with their wild-type littermates...
February 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Cong-Lin Liu, Yi Wang, Mengyang Liao, Holger Wemmelund, Jingyuan Ren, Cleverson Fernandes, Yi Zhou, Galina K Sukhova, Jes S Lindholt, Søren P Johnsen, Jin-Ying Zhang, Xiang Cheng, Xiaozhu Huang, Alan Daugherty, Bruce D Levy, Peter Libby, Guo-Ping Shi
OBJECTIVE: Asthma and abdominal aortic aneurysms (AAA) both involve inflammation. Patients with asthma have an increased risk of developing AAA or experiencing aortic rupture. This study tests the development of one disease on the progression of the other. APPROACH AND RESULTS: Ovalbumin sensitization and challenge in mice led to the development of allergic lung inflammation (ALI). Subcutaneous infusion of angiotensin II into mice produced AAA. Simultaneous production of ALI in AAA mice doubled abdominal aortic diameter and increased macrophage and mast cell content, arterial media smooth muscle cell loss, cell proliferation, and angiogenesis in AAA lesions...
January 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Elliott M Antman, Emelia J Benjamin, Robert A Harrington, Steven R Houser, Eric D Peterson, Mary Ann Bauman, Nancy Brown, Vincent Bufalino, Robert M Califf, Mark A Creager, Alan Daugherty, David L Demets, Bernard P Dennis, Shahram Ebadollahi, Mariell Jessup, Michael S Lauer, Bernard Lo, Calum A MacRae, Michael V McConnell, Alexa T McCray, Michelle M Mello, Eric Mueller, Jane W Newburger, Sally Okun, Milton Packer, Anthony Philippakis, Peipei Ping, Prad Prasoon, Véronique L Roger, Steve Singer, Robert Temple, Melanie B Turner, Kevin Vigilante, John Warner, Patrick Wayte
BACKGROUND: A 1.5-day interactive forum was convened to discuss critical issues in the acquisition, analysis, and sharing of data in the field of cardiovascular and stroke science. The discussion will serve as the foundation for the American Heart Association's (AHA's) near-term and future strategies in the Big Data area. The concepts evolving from this forum may also inform other fields of medicine and science. METHODS AND RESULTS: A total of 47 participants representing stakeholders from 7 domains (patients, basic scientists, clinical investigators, population researchers, clinicians and healthcare system administrators, industry, and regulatory authorities) participated in the conference...
November 2015: Journal of the American Heart Association
Hong Lu, Deborah A Howatt, Anju Balakrishnan, Jessica J Moorleghen, Debra L Rateri, Lisa A Cassis, Alan Daugherty
Osmotic pumps continuously deliver compounds at a constant rate into small animals. This article introduces a standard protocol used to induce aortic aneurysms via subcutaneous infusion of angiotensin II (AngII) from implanted osmotic pumps. This protocol includes calculation of AngII amount and dissolution, osmotic pump filling, implantation of osmotic pumps subcutaneously, observation after pump implantation, and harvest of aortas to visualize aortic aneurysms in mice. Subcutaneous infusion of AngII through osmotic pumps following this protocol is a reliable and reproducible technique to induce both abdominal and thoracic aortic aneurysms in mice...
2015: Journal of Visualized Experiments: JoVE
Frank M Davis, Debra L Rateri, Alan Daugherty
PURPOSE OF REVIEW: Abdominal aortic aneurysm (AAA) is a pathological condition of permanent dilation that portends the potentially fatal consequence of aortic rupture. This review emphasizes recent advances in mechanistic insight into aneurysm pathogenesis and potential pharmacologic therapies that are on the horizon for AAAs. RECENT FINDINGS: An increasing body of evidence demonstrates that genetic factors, including 3p12.3, DAB2IP, LDLr, LRP1, matrix metalloproteinase (MMP)-3, TGFBR2, and SORT1 loci, are associated with AAA development...
November 2015: Current Opinion in Cardiology
Hong Lu, Alan Daugherty
No abstract text is available yet for this article.
October 2015: Current Opinion in Lipidology
Jing Liu, Alan Daugherty, Hong Lu
Abdominal aortic aneurysm (AAA) is a devastating disease associated with high prevalence of death due to aortic rupture. Currently the therapy is restricted to surgical procedures to prevent aortic rupture, which in turn has a risk for postoperative mortality. There are no proven pharmacological therapies available to prevent expansion or rupture of AAA due to the paucity of knowledge on the mechanisms underlying the nature and pathophysiological processes of this complex disease. Animal models are powerful tools to provide mechanistic insights into understanding the development of AAA...
2015: Current Pharmaceutical Design
Aruna Poduri, Debra L Rateri, Deborah A Howatt, Anju Balakrishnan, Jessica J Moorleghen, Lisa A Cassis, Alan Daugherty
OBJECTIVE: Angiotensin II (Ang II) infusion causes aortic medial thickening via stimulation of angiotensin II type 1a (AT1a) receptors. The purpose of this study was to determine the cellular loci of AT1a receptors that mediate this Ang II-induced aortic pathology. APPROACH AND RESULTS: Saline or Ang II was infused into AT1a receptor floxed mice expressing Cre under control of cell-specific promoters. Initially, AT1a receptors were depleted in aortic smooth muscle cell and endothelium by expressing Cre under control of SM22 and Tie2 promoters, respectively...
September 2015: Arteriosclerosis, Thrombosis, and Vascular Biology
A Phillip Owens, Todd L Edwards, Silvio Antoniak, Julia E Geddings, Eiman Jahangir, Wei-Qi Wei, Joshua C Denny, Yacine Boulaftali, Wolfgang Bergmeier, Alan Daugherty, Uchechukwu K A Sampson, Nigel Mackman
OBJECTIVE: Rupture of abdominal aortic aneurysms causes a high morbidity and mortality in the elderly population. Platelet-rich thrombi form on the surface of aneurysms and may contribute to disease progression. In this study, we used a pharmacological approach to examine a role of platelets in established aneurysms induced by angiotensin II infusion into hypercholesterolemic mice. APPROACH AND RESULTS: Administration of the platelet inhibitors aspirin or clopidogrel bisulfate to established abdominal aortic aneurysms dramatically reduced rupture...
September 2015: Arteriosclerosis, Thrombosis, and Vascular Biology
Sean E Thatcher, Xuan Zhang, Shannon Woody, Yu Wang, Yasir Alsiraj, Richard Charnigo, Alan Daugherty, Lisa A Cassis
BACKGROUND: Abdominal aortic aneurysms (AAAs) occur predominately in males. However, AAAs in females have rapid growth rates and rupture at smaller sizes. Mechanisms contributing to AAA progression in females are undefined. We defined effects of ovariectomy, with and without 17-β estradiol (E2), on progression of established angiotensin II (AngII)-induced AAAs in female mice. METHODS: We used neonatal testosterone exposures at 1 day of age to promote susceptibility to AngII-induced AAAs in adult female Ldlr (-/-) mice...
2015: Biology of Sex Differences
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