2023
FN (Fibronectin)-Integrin α5 Signaling Promotes Thoracic Aortic Aneurysm in a Mouse Model of Marfan Syndrome
Chen M, Cavinato C, Hansen J, Tanaka K, Ren P, Hassab A, Li D, Youshao E, Tellides G, Iyengar R, Humphrey J, Schwartz M. FN (Fibronectin)-Integrin α5 Signaling Promotes Thoracic Aortic Aneurysm in a Mouse Model of Marfan Syndrome. Arteriosclerosis Thrombosis And Vascular Biology 2023, 43: e132-e150. PMID: 36994727, PMCID: PMC10133209, DOI: 10.1161/atvbaha.123.319120.Peer-Reviewed Original ResearchConceptsContractile gene expressionSmooth muscle cellsGene expressionMgR miceWild-type smooth muscle cellsMarfan miceAortic aneurysmMouse modelMarfan syndromeMouse aortic smooth muscle cellsPathogenesis of TAACytoplasmic domainVascular smooth muscle cellsThoracic aortic aneurysmAortic smooth muscle cellsCultured smooth muscle cellsNF-kB activationNF-kB inhibitionMolecular mechanismsIntegrin α2ECM remodelingElastic fiber integrityPhenotypic modulationMarfan's aneurysmsMgR/
2022
mTOR inhibition prevents angiotensin II–induced aortic rupture and pseudoaneurysm but promotes dissection in Apoe-deficient mice
He C, Jiang B, Wang M, Ren P, Murtada SI, Caulk AW, Li G, Qin L, Assi R, Lovoulos CJ, Schwartz MA, Humphrey JD, Tellides G. mTOR inhibition prevents angiotensin II–induced aortic rupture and pseudoaneurysm but promotes dissection in Apoe-deficient mice. JCI Insight 2022, 7: e155815. PMID: 35132962, PMCID: PMC8855820, DOI: 10.1172/jci.insight.155815.Peer-Reviewed Original ResearchConceptsApoE-deficient miceAngiotensin IIVascular wall cellsAortic tearAortic ruptureMTOR inhibitionSmooth muscle cell hypertrophyMatricellular proteinWall cellsSuprarenal abdominal aortaMuscle cell hypertrophyExtracellular matrix accumulationInhibition of mTORRole of mTORSubadventitial hematomaFree ruptureAortic dissectionAortic diseaseAortic aneurysmSignificant dissectionAbdominal aortaHemorrhagic lesionsExtensive dissectionMetalloproteinase expressionCell hypertrophy
2015
Role of Mechanotransduction in Vascular Biology
Humphrey JD, Schwartz MA, Tellides G, Milewicz DM. Role of Mechanotransduction in Vascular Biology. Circulation Research 2015, 116: 1448-1461. PMID: 25858068, PMCID: PMC4420625, DOI: 10.1161/circresaha.114.304936.Peer-Reviewed Original ResearchConceptsExtracellular matrixRole of mechanotransductionExtracellular matrix constituentsActomyosin filamentsMembrane receptorsDysfunctional mechanosensingVascular biologyAortic aneurysmNew therapeutic strategiesContractile proteinsThoracic aortic aneurysmIntramural cellsCellsMechanobiological processesMatrix constituentsAcute dissectionAortic cellsAortic diseaseMechanosensingTherapeutic strategiesHemodynamic loadGenesProgressive enlargementReceptorsMechanoregulation
2014
Dysfunctional Mechanosensing in Aneurysms
Humphrey JD, Milewicz DM, Tellides G, Schwartz MA. Dysfunctional Mechanosensing in Aneurysms. Science 2014, 344: 477-479. PMID: 24786066, PMCID: PMC4360903, DOI: 10.1126/science.1253026.Peer-Reviewed Original Research