Transthyretin amyloid fibrils alter primary fibroblast structure, function, and inflammatory gene expression
Kyle Dittloff, Antonio Iezzi, Justin X. Zhong, Priya Mohindra, Tejal A. Desai, Brenda Russell
Abstract
Transthyretin (TTR) cardiac amyloidosis involves deposition of fibrils of misfolded TTR in the aging human heart, leading to cardiac dysfunction and heart failure. Our novel in vitro studies show that TTR fibrils alter primary cardiac fibroblast cytoskeletal and nuclear structure and focal adhesion formation. Furthermore, both fibrillar and tetrameric TTR significantly increased cellular migration velocity and caused upregulation of inflammatory genes determined by transcriptomic RNA and protein analysis. These findings may suggest new therapeutic approaches.
Topics & Concepts
TransthyretinAmyloid fibrilAmyloid (mycology)Primary (astronomy)FibrilChemistryAmyloidosisFibroblastFunction (biology)InflammationGeneCell biologyBiochemistryPathologyBiologyMedicineImmunologyAmyloid βDiseasePhysicsIn vitroInorganic chemistryAstronomyAmyloidosis: Diagnosis, Treatment, OutcomesCellular transport and secretionAlzheimer's disease research and treatments