2024
TTN truncation variants produce sarcomere-integrating proteins of uncertain functional significance
Hinson J, Campbell S. TTN truncation variants produce sarcomere-integrating proteins of uncertain functional significance. Journal Of Clinical Investigation 2024, 134: e175206. PMID: 38226618, PMCID: PMC10786689, DOI: 10.1172/jci175206.Peer-Reviewed Original ResearchConceptsTruncating variantsSubcellular localizationTitin truncating variantsComplex proteinsSarcomere integrityGenetic lesionsTitin proteinDilated cardiomyopathyFunctional consequencesProteinVariable penetranceSarcomeric dysfunctionImpaired cardiac contractilityTitinSarcomeric structural integrityAlternative therapeutic approachCardiac contractilityVariantsPotential mechanismsTherapeutic approachesHaploinsufficiencyDCM samples
2022
Muscle LIM Protein Force-Sensing Mediates Sarcomeric Biomechanical Signaling in Human Familial Hypertrophic Cardiomyopathy
Riaz M, Park J, Sewanan LR, Ren Y, Schwan J, Das SK, Pomianowski PT, Huang Y, Ellis MW, Luo J, Liu J, Song L, Chen IP, Qiu C, Yazawa M, Tellides G, Hwa J, Young LH, Yang L, Marboe CC, Jacoby DL, Campbell SG, Qyang Y. Muscle LIM Protein Force-Sensing Mediates Sarcomeric Biomechanical Signaling in Human Familial Hypertrophic Cardiomyopathy. Circulation 2022, 145: 1238-1253. PMID: 35384713, PMCID: PMC9109819, DOI: 10.1161/circulationaha.121.056265.Peer-Reviewed Original ResearchConceptsHypertrophic cardiomyopathySarcomeric mutationsFamilial hypertrophic cardiomyopathySudden cardiac deathCardiac myosin heavy chainMechanism-based treatmentsDevelopment of hypertrophyActivated T cellsCalcineurin-nuclear factorForce productionPhenotypic expressionPluripotent stem cell-derived cardiomyocytesStem cell-derived cardiomyocytesHeart failureCardiac deathVentricular hypertrophyCell-derived cardiomyocytesCardiac contractilityPharmacological interventionsT cellsCardiac diseaseCardiac hypertrophyPatient-specific induced pluripotent stem cellsPharmacological meansTwitch relaxation