Murine models of sickle cell disease and beta-thalassemia demonstrate pulmonary hypertension with distinctive features.
Murine models of sickle cell disease and beta-thalassemia demonstrate pulmonary hypertension with distinctive features.
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DOI：
10.1177/20458940211055996
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发表时间：
2021-10
影响因子：
2.6
通讯作者：
Irwin DC
中科院分区：
文献类型：
--
作者：
Buehler PW;Swindle D;Pak DI;Fini MA;Hassell K;Nuss R;Wilkerson RB;D'Alessandro A;Irwin DC
镰状细胞性贫血和中间β-地中海贫血是两种非常不同的遗传性血红蛋白疾病，易导致肺动脉高压。导致这两种疾病相关的肺动脉高压的病因是多因素的，并描述了广泛的机制因素。镰状细胞性贫血和β-地中海贫血均表现为血管内和血管外溶血。由于镰状细胞性贫血和中间型β-地中海贫血具有血管外溶血、巨噬细胞铁过量和贫血的共同特征，我们试图表征肺动脉高压的表型、心脏力学和功能以及肺和右室代谢的共同特征。在铁的概念中，我们定义了一种独特的肺血管铁积聚在镰状细胞性贫血肺动脉高压患者的尸检中。这一观察结果与特发性或其他形式的肺动脉高压不同。在这项研究中，我们假设一个共同的病理生理学特征将表征镰状细胞性贫血和β-中间型地中海贫血小鼠模型的肺动脉高压表型。然而，与镰状细胞性贫血不同，β-地中海贫血也是一种红细胞生成障碍的疾病，铁吸收增加，细胞铁排出。这一过程是由高铁蛋白和低海普西丁水平以及转铁蛋白饱和引起的铁转运失调所介导的，因此也可能存在差异。在这里，我们描述了老年BERK-SS(镰状细胞性贫血)和HBBTH/3+(中度β-地中海贫血)小鼠的共同和不同的肺动脉高压特征，并建议将翻译效用作为概念验证模型来研究遗传性贫血的肺动脉高压治疗。
Sickle cell anemia and β-thalassemia intermedia are very different genetically determined hemoglobinopathies predisposing to pulmonary hypertension. The etiologies responsible for the associated development of pulmonary hypertension in both diseases are multi-factorial with extensive mechanistic contributors described. Both sickle cell anemia and β-thalassemia intermedia present with intra and extravascular hemolysis. And because sickle cell anemia and β-thalassemia intermedia share features of extravascular hemolysis, macrophage iron excess and anemia we sought to characterize the common features of the pulmonary hypertension phenotype, cardiac mechanics, and function as well as lung and right ventricular metabolism. Within the concept of iron, we have defined a unique pulmonary vascular iron accumulation in lungs of sickle cell anemia pulmonary hypertension patients at autopsy. This observation is unlike findings in idiopathic or other forms of pulmonary arterial hypertension. In this study, we hypothesized that a common pathophysiology would characterize the pulmonary hypertension phenotype in sickle cell anemia and β-thalassemia intermedia murine models. However, unlike sickle cell anemia, β-thalassemia is also a disease of dyserythropoiesis, with increased iron absorption and cellular iron extrusion. This process is mediated by high erythroferrone and low hepcidin levels as well as dysregulated iron transport due transferrin saturation, so there may be differences as well. Herein we describe common and divergent features of pulmonary hypertension in aged Berk-ss (sickle cell anemia) and Hbbth/3+ (intermediate β-thalassemia) mice and suggest translational utility as proof-of-concept models to study pulmonary hypertension therapeutics specific to genetic anemias.
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影响因子：
4
作者：
Catala, Alexis;Youssef, Lyla A.;D'Alessandro, Angelo
通讯作者：
D'Alessandro, Angelo
DOI：
10.1161/hypertensionaha.120.14772
发表时间：
2020-08
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Kitagawa A;Kizub I;Jacob C;Michael K;D'Alessandro A;Reisz JA;Grzybowski M;Geurts AM;Rocic P;Gupte R;Miano JM;Gupte SA
通讯作者：
Gupte SA
影响因子：
9.6
作者：
Machado, Roberto F.;Gladwin, Mark T.
通讯作者：
Gladwin, Mark T.
影响因子：
20.3
作者：
Hsu, Lewis L.;Champion, Hunter C.;Gladwin, Mark T.
通讯作者：
Gladwin, Mark T.
影响因子：
64.8
作者：
通讯作者：
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