title: Transthyretin cardiac amyloidosis: pathogenesis, treatments, and emerging role in heart failure with preserved ejection fraction.
abstract: Transthyretin (TTR) amyloidosis causes heart failure from cardiac deposition of TTR amyloid fibrils, the by-product of TTR homotetramer disassembly. Wild-type (WT) TTR deposition leads to senile amyloidosis, predominantly manifesting with cardiomyopathy. Missense mutations in the TTR gene result in familial TTR amyloidosis. Certain mutations are more likely to affect the heart, while others cause more neurologic involvement. Extracellular fibril deposition triggers intracellular stress response, upregulation of the inflammatory cascades, apoptosis, and organ dysfunction. Recent studies suggest that TTR cardiac amyloid may be a significant contributor to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Summarized in this review are the molecular pathways underlying the cellular toxicity of TTR amyloid fibrils and the emerging therapies aimed at TTR tetramer stabilization, abrogation of TTR synthesis in the liver, or inhibition of amyloidogenesis.
authors: Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA.
authors: Van-Khue
authors: VK
authors: Ton
authors: Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA.
authors: Monica
authors: M
authors: Mukherjee
authors: Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA.
authors: Daniel P
authors: DP
authors: Judge
keywords: cardiac amyloidosis; heart failure with preserved ejection fraction (HFpEF); transthyretin (TTR)
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