About the Lab
Under the supervision of Ying H. Shen, M.D., Ph.D., the aortic disease research team pursues several research projects and maintains one of the world’s most extensive and well-cataloged aortic tissue banks. This core resource facilitates investigations into the causes and progression of aortic disease pursued by our researchers, as well as researchers from other academic institutions.
The members of the lab employ a wide range of standard and advanced techniques, including tissue analysis, cell-based experiments, mouse models of aortic disease, and single-cell transcriptome analysis. Through an American Heart Association Strategically Focused Vascular Research Network Award, the lab has established the Aortopathy Research Center in partnership with collaborators at the University of Kentucky College of Medicine. The goal of this project is to understand how different types of cells in the aortic wall respond to stress and how these responses differ in men and women.
Publications
Chakraborty A, Li Y, Zhang C, Li Y, Rebello KR, Li S, Xu S, Vasquez HG, Zhang L, Luo W, Wang G, Chen K, Coselli JS, LeMaire SA, Shen YH. "Epigenetic Induction of Smooth Muscle Cell Phenotypic Alterations in Aortic Aneurysms and Dissections." Circulation. 2023 Sep 19;142:959-977. Pubmed PMID: 37555319
Zhang C, Li Y, Chakraborty A, Li Y, Rebello KR, Ren P, Luo W, Zhang L, Lu HS, Cassis LA, Coselli JS, Daugherty A, LeMaire SA, Shen YH. "Aortic Stress Activates an Adaptive Program in Thoracic Aortic Smooth Muscle Cells That Maintains Aortic Strength and Protects Against Aneurysm and Dissection in Mice.." Arterioscler Thromb Vasc Biol.. 2023 Feb;43(2):234-252. Pubmed PMID: 36579645
LeMaire SA, Zhang L, Zhang NS, Luo W, Barrish JP, Zhang Q, Coselli JS, Shen YH. "Ciprofloxacin accelerates aortic enlargement and promotes dissection and rupture in Marfan mice.." J Thorac Cardiovasc Surg. 2022 Mar;163(3):e215-e226.
Li Y, Ren P, Dawson A, Vasquez HG, Ageedi W, Zhang C, Luo W, Chen R, Li Y, Kim S, Lu HS, Cassis LA, Coselli JS, Daugherty A, Shen YH, LeMaire SA. "Single-Cell Transcriptome Analysis Reveals Dynamic Cell Populations and Differential Gene Expression Patterns in Control and Aneurysmal Human Aortic Tissue." Circulation. 2020 Oct;142(14):1374-1388. Pubmed PMID: 33017217
Luo W, Wang Y, Zhang L, Ren P, Zhang C, Li Y, Azares AR, Zhang M, Guo J, Ghaghada KB, Starosolski ZA, Rajapakshe K, Coarfa C, Li Y, Chen R, Fujiwara K, Abe JI, Coselli JS, Milewicz DM, LeMaire SA, Shen YH "Critical Role of Cytosolic DNA and Its Sensing Adaptor STING in Aortic Degeneration, Dissection, and Rupture." Circulation. 2020 Jan;141(1):42-66. Pubmed PMID: 31887080
LeMaire SA, Zhang L, Luo W, Ren P, Azares AR, Wang Y, Zhang C, Coselli JS, Shen YH. "Effect of Ciprofloxacin on Susceptibility to Aortic Dissection and Rupture in Mice.." JAMA Surg. 2018 Sep;153(9):e181804.. Pubmed PMID: 30046809
Wu D, Ren P, Zheng Y, Zhang L, Xu G, Xie W, Lloyd EE, Zhang S, Zhang Q, Curci JA, Coselli JS, Milewicz DM, Shen YH, LeMaire SA. "NLRP3 (Nucleotide Oligomerization Domain-Like Receptor Family, Pyrin Domain Containing 3)-Caspase-1 Inflammasome Degrades Contractile Proteins: Implications for Aortic Biomechanical Dysfunction and Aneurysm and Dissection Formation.." Arterioscler Thromb Vasc Biol. 2017 Apr;37(4):694-706. Pubmed PMID: 28153878
Mao Y, Luo W, Zhang L, Wu W, Yuan L, Xu H, Song J, Fujiwara K, Abe JI, LeMaire SA, Wang XL, Shen YH. "STING–IRF3 Triggers Endothelial Inflammation in Response to Free Fatty Acid-Induced Mitochondrial Damage in Diet-Induced Obesity." Arterioscler Thromb Vasc Biol.. 2017 May;37(5):920-929. Pubmed PMID: 28302626
Yuan L, Mao Y, Luo W, Wu W, Xu H, Wang XL, Shen YH "Palmitic acid dysregulates the Hippo-YAP pathway and inhibits angiogenesis by inducing mitochondrial damage and activating the cytosolic DNA sensor cGAS-STING-IRF3 signaling mechanism.." J Biol Chem. 2017 Sep;292(36):15002-15015. Pubmed PMID: 28698384
Ren P, Hughes M, Krishnamoorthy S, Zou S, Zhang L, Wu D, Zhang C, Curci JA, Coselli JS, Milewicz DM, LeMaire SA, Shen YH. "Critical Role of ADAMTS-4 in the Development of Sporadic Aortic Aneurysm and Dissection in Mice.." Sci Rep. 2017 Sep 27;7(1)::12351.. Pubmed PMID: 28955046
Shen YH, Zhang L, Ren P, Nguyen MT, Zou S, Wu D, Wang XL, Coselli JS, Lemaire SA "AKT2 Confers Protection Against Aortic Aneurysms and Dissections." Circ Res. 2013 Feb;112(4):618-32. Pubmed PMID: 23250987
Li XN, Song J, Zhang L, LeMaire SA, Hou X, Zhang C, Coselli JS, Chen L, Wang XL, Zhang Y, Shen YH "Activation of the AMPK-FOXO3 pathway reduces fatty acid-induced increase in intracellular reactive oxygen species by upregulating thioredoxin.." Diabetes. 2009 Oct;58(10):2246-57. Pubmed PMID: 19592618
Wang XL, Zhang L, Youker K, Zhang MX, Wang J, LeMaire SA, Coselli JS, Shen YH "Free fatty acids inhibit insulin signaling-stimulated endothelial nitric oxide synthase activation through upregulating PTEN or inhibiting Akt kinase." Diabetes. 2006 Aug;55(8):2301-10. Pubmed PMID: 16873694
Shen YH, Utama B, Wang J, Raveendran M, Duraisamy S, Waldman WJ, Belcher J, Vercellotti G, Martin D, Mitchelle B, Wang XL "Human cytomegalovirus causes endothelial injury through the ataxia telangiectasia mutant and p53 DNA damage signaling pathways." Circ Res. 2004 May;94(10):1310-7. Pubmed PMID: 15105295
Ren P, Wu D, Appel R, Zhang L, Zhang C, Luo W, Robertson AAB, Cooper MA, Coselli JS, Milewicz DM, Shen YH, LeMaire SA. Targeting the NLRP3 Inflammasome With Inhibitor MCC950 Prevents Aortic Aneurysms and Dissections in Mice. J Am Heart Assoc. 2020 Apr 7;9(7). PubMed PMID: 32223388.
Luo W, Wang Y, Zhang L, Ren P, Zhang C, Li Y, Azares AR, Zhang M, Guo J, Ghaghada KB, Starosolski ZA, Rajapakshe K, Coarfa C, Li Y, Chen R, Fujiwara K, Abe JI, Coselli JS, Milewicz DM, LeMaire SA, Shen YH. Critical Role of Cytosolic DNA and Its Sensing Adaptor STING in Aortic Degeneration, Dissection, and Rupture. Circulation. 2020 Jan 7;141(1):42-66. PMID: 31887080.
Ren P, Hughes M, Krishnamoorthy S, Zou S, Zhang L, Wu D, Zhang C, Curci JA, Coselli JS, Milewicz DM, LeMaire SA, Shen YH. Critical role of ADAMTS-4 in the development of sporadic aortic aneurysm and dissection in mice. Sci Rep. 2017 Sep 27;7(1):12351. PMID: 28955046.
LeMaire SA, Zhang L, Luo W, Ren P, Azares, AR, Wang Y, Zhang C, Coselli JS, Shen YH. Ciprofloxacin increases susceptibility to aortic dissection and rupture in mice. JAMA Surgery, 2018 Jul 25:e181804. PMID: 30046809.
Wu D, Ren P, Zheng Y, Zhang L, Xu G, Xie W, Lloyd EE, Zhang S, Zhang Q, Curci JA, Coselli JS, Milewicz DM, Shen YH, LeMaire SA. NLRP3 (nucleotide oligomerization domain-like receptor family, pyrin domain containing 3)-caspase-1 inflammasome degrades contractile proteins: implications for aortic biomechanical dysfunction and aneurysm and dissection formation. Arterioscler Thromb Vasc Biol. 2017 Apr;37(4):694-706. PMID:28153878.
Albini PT, Segura AM, Liu G, Minard CG, Coselli JS, Milewicz DM, Shen YH, LeMaire SA. Advanced atherosclerosis is associated with increased medial degeneration in sporadic ascending aortic aneurysms. Atherosclerosis. 2014 Feb;232(2):361-8. PubMed PMID: 24468149.
Shen YH , Zhang L, Ren P, Nguyen MT, Zou S, Wu D, Wang XL, Coselli J, LeMaire SA. AKT2 confers protection against aortic aneurysms and dissections. Circ Res 2013;112:618-32. PMID: 23250987.
Ren P, Zhang L, Xu G, Palmero LC, Albini PT, Coselli JS, Shen YH, LeMaire SA. ADAMTS-1 and ADAMTS-4 levels are elevated in thoracic aortic aneurysms and dissections. Ann Thorac Surg. 2013 Feb;95(2):570-7. PubMed PMID: 23245439.
Zou S, Ren P, Nguyen M, Coselli JS, Shen YH, LeMaire SA. Notch signaling in descending thoracic aortic aneurysm and dissection. PLoS One. 2012;7(12):e52833. doi: 10.1371/journal.pone.0052833. PMID: 23300792; PubMed Central PMCID: PMC3530510.
LeMaire SA, McDonald MLN, Guo DC, Russell L, Miller CC III, Johnson RJ, Bekheirnia MR, Franco LM, Nguyen M, Pyeritz RE, Bavaria JE, Devereux R, Maslen C, Holmes KW, Eagle K, Body SC, Seidman C, Seidman JG, Isselbacher EM, Bray M, Coselli JS, Estrera AL, Safi HJ, Belmont JW, Leal SM, Milewicz DM. Genome-wide association study identifies a susceptibility locus for thoracic aortic aneurysms and aortic dissections spanning FBN1 at 15q21.1. Nat Genet 2011; 43: 996-1000.