Novel molecular insights into V122I transthyretin cardiac amyloidosis: A critical yet underdiagnosed cause of Heart Fail

Project: Research

Investigators

  • Kevin Alexander (PI)

Description

Full Title: Novel molecular insights into V122I transthyretin cardiac amyloidosis: A critical yet underdiagnosed cause of heart failure in African AmericansSummaryTransthyretin cardiac amyloidosis is an important, but underdiagnosed cause ofheart failure with preserved ejection fraction. Over a million African Americans inthe United States carry the V122I transthyretin mutation, which significantlyincreases the risk of developing this deadly disease. The pathogenesis oftransthyretin amyloidosis remains poorly understood, and no approvedtreatments are available. The goal of this proposal is to use a novel in vivomouse model and a cohort of patient samples to elucidate the precise molecularmechanisms by which V122I transthyretin leads to cardiac amyloidosis and heartfailure. I will test the hypotheses that 1) biomechanical stress promotes V122Itransthyretin instability and amyloid formation and 2) V122I transthyretin causesdirect cardiotoxicity independent of amyloid fibril deposition.
Award amount$420,000.00
Award date07/01/2019
Program typeAHA AMFDP Scholar
Award ID19AMFDP34990036
Effective start/end date07/01/201906/30/2023
StatusActive