Stanciu Silviu Marcel, Jurcut Ruxandra, Dragoi Galrinho Ruxandra, Stefani Constantin, Miricescu Daniela, Rusu Ioana Ruxandra, Prisacariu Georgiana Sabina, Mititelu Raluca
Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacy, Central Military Emergency University Hospital, 010825 Bucharest, Romania.
Department of Cardiology, Carol Davila University of Medicine and Pharmacy, Institute of Cardiovascular Diseases "Prof CC Iliescu", 022322 Bucharest, Romania.
Int J Mol Sci. 2024 Dec 27;26(1):146. doi: 10.3390/ijms26010146.
Amyloidosis is a rare pathology characterized by protein deposits in various organs and tissues. Cardiac amyloidosis (CA) can be caused by various protein deposits, but transthyretin amyloidosis (ATTR) and immunoglobulin light chain (AL) are the most frequent pathologies. Protein misfolding can be induced by several factors such as oxidative stress, genetic mutations, aging, chronic inflammation, and neoplastic disorders. In ATTR cardiomyopathy (ATTR-CM), the amyloid fibrils can be found in the myocardium interstitial space and are associated with arrhythmias and heart failure. In pathological situations, the transthyretin (TTR) configuration is destroyed by proteolytic action, leading to monomers that further misfold and aggregate to form the amyloid fibrils. Tc-Pyrophosphate (-Tc-PYP), Tc 3,3-diphosphono-1,2-propanodicarboxylic acid (-Tc-DPD) and -Tc hydroxy-methylene-Dyphosphonate (-Tc-HMDP) are used to detect myocardium amyloid deposits due to their ability to detect calcium ions that are present in the amyloid fibrils through dystrophic calcification. ATTR-CM therapy acts on different stages of the amyloidogenic process, including liver TTR synthesis, TTR tetramer destabilization, and misfolding of the monomers. The main aim of this narrative review is to present ATTR-CM, starting with molecular changes regarding the protein misfolding process and radionuclide aspects and finishing with pharmacological approaches.
淀粉样变性是一种罕见的病理学疾病，其特征是在各种器官和组织中存在蛋白质沉积。心脏淀粉样变性（CA）可由多种蛋白质沉积引起，但转甲状腺素蛋白淀粉样变性（ATTR）和免疫球蛋白轻链（AL）是最常见的病理类型。蛋白质错误折叠可由多种因素诱导，如氧化应激、基因突变、衰老、慢性炎症和肿瘤性疾病。在ATTR心肌病（ATTR-CM）中，淀粉样纤维可在心肌间质空间中发现，并与心律失常和心力衰竭相关。在病理情况下，转甲状腺素蛋白（TTR）的结构被蛋白水解作用破坏，导致单体进一步错误折叠并聚集形成淀粉样纤维。锝-焦磷酸盐（-Tc-PYP）、锝-3,3-二膦酰基-1,2-丙二酸（-Tc-DPD）和锝-羟基亚甲基二膦酸盐（-Tc-HMDP）用于检测心肌淀粉样沉积物，因为它们能够通过营养不良性钙化检测淀粉样纤维中存在的钙离子。ATTR-CM治疗作用于淀粉样蛋白生成过程的不同阶段，包括肝脏TTR合成、TTR四聚体不稳定和单体错误折叠。本叙述性综述的主要目的是介绍ATTR-CM，从蛋白质错误折叠过程的分子变化和放射性核素方面开始，以药理学方法结束。
