Biomechanical and transcriptional evidence that smooth muscle cell death drives an osteochondrogenic phenotype and severe proximal vascular disease in progeria
Murtada S, Kawamura Y, Cavinato C, Wang M, Ramachandra A, Spronck B, Li D, Tellides G, Humphrey J. Biomechanical and transcriptional evidence that smooth muscle cell death drives an osteochondrogenic phenotype and severe proximal vascular disease in progeria. Biomechanics And Modeling In Mechanobiology 2023, 22: 1333-1347. PMID: 37149823, PMCID: PMC10544720, DOI: 10.1007/s10237-023-01722-5.Peer-Reviewed Original ResearchConceptsPulse wave velocitySmooth muscle cell deathMuscle cell deathDisease processOsteochondrogenic phenotypeAdverse extracellular matrix remodelingImportant cardiovascular implicationsProgressive aortic diseaseProximal elastic arteriesVentricular diastolic dysfunctionProgressive disease processSmooth muscle cellsCell deathCardiovascular sequelaeDiastolic dysfunctionCardiovascular implicationsExtracellular matrix remodelingAortic diseasePrimary diagnosisVascular diseaseAccumulation of proteoglycansMuscular arteriesAortic structureAortic wallLate calcificationLonafarnib improves cardiovascular function and survival in a mouse model of Hutchinson-Gilford progeria syndrome
Murtada S, Mikush N, Wang M, Ren P, Kawamura Y, Ramachandra A, Li D, Braddock D, Tellides G, Gordon L, Humphrey J. Lonafarnib improves cardiovascular function and survival in a mouse model of Hutchinson-Gilford progeria syndrome. ELife 2023, 12: e82728. PMID: 36930696, PMCID: PMC10023154, DOI: 10.7554/elife.82728.Peer-Reviewed Original ResearchConceptsMouse modelLeft ventricular diastolic functionHutchinson-Gilford progeria syndromeVentricular diastolic functionPulse wave velocityDrug-associated effectsMTOR inhibitor rapamycinCardiovascular sequelaeDiastolic functionProgeria syndromeDevastating conditionCardiac functionCardiovascular functionClinical trialsCardiovascular diseaseMuscular arteriesUS FoodDrug AdministrationProgeria miceArterial structurePremature deathLonafarnibCardiovascular structureCharacteristics of agingInhibitor rapamycin