Circulatory contributors to the phenotype in hereditary hemorrhagic telangiectasia
Circulatory contributors to the phenotype in hereditary hemorrhagic telangiectasia
复制标题
遗传性出血性毛细血管扩张症表型的循环因素
作者：
C. Shovlin
遗传性出血性毛细血管扩张（HHT）在机制和治疗上都具有挑战性，不仅因为分子和细胞的扰动会导致血管异常，而且还会导致循环生理的改变，并可能加剧血管损伤。首先，大多数HHT患者有内脏动静脉畸形（avm）。明显的内脏avm降低了全身血管阻力：维持动脉血压需要超正常的心输出量，并可能导致明显的肺静脉高压。其次，鼻腔和胃肠道毛细血管扩张引起的出血导致铁的大量流失，在大多数情况下，饮食不足以满足出血调节的铁需求。由此导致的缺铁限制了红细胞生成，导致贫血和心输出量进一步增加。低铁水平也与静脉和动脉血栓形成、因子VIII升高和循环5HT（血清素）血小板聚集增加有关。第三，最近的数据强调，由于肺动脉动静脉畸形导致血液氧合减少，导致分级红细胞反应以维持动脉血氧含量，并导致更高的搏量和/或心率以维持氧气输送。最后，与HHT无关的因素，如饮食、妊娠、败血症和其他并发疾病也会影响HHT患者的血管结构、出血和铁处理。这些考虑强调了影响HHT血管结构的机制的复杂性，也为靶向治疗方法提供了机会。
Hereditary hemorrhagic telangiectasia (HHT) is mechanistically and therapeutically challenging, not only because of the molecular and cellular perturbations that generate vascular abnormalities, but also the modifications to circulatory physiology that result, and are likely to exacerbate vascular injury. First, most HHT patients have visceral arteriovenous malformations (AVMs). Significant visceral AVMs reduce the systemic vascular resistance: supra-normal cardiac outputs are required to maintain arterial blood pressure, and may result in significant pulmonary venous hypertension. Secondly, bleeding from nasal and gastrointestinal telangiectasia leads to iron losses of such magnitude that in most cases, diet is insufficient to meet the ‘hemorrhage adjusted iron requirement.’ Resultant iron deficiency restricts erythropoiesis, leading to anemia and further increases in cardiac output. Low iron levels are also associated with venous and arterial thromboses, elevated Factor VIII, and increased platelet aggregation to circulating 5HT (serotonin). Third, recent data highlight that reduced oxygenation of blood due to pulmonary AVMs results in a graded erythrocytotic response to maintain arterial oxygen content, and higher stroke volumes and/or heart rates to maintain oxygen delivery. Finally, HHT-independent factors such as diet, pregnancy, sepsis, and other intercurrent illnesses also influence vascular structures, hemorrhage, and iron handling in HHT patients. These considerations emphasize the complexity of mechanisms that impact on vascular structures in HHT, and also offer opportunities for targeted therapeutic approaches.
影响因子：
4.3
作者：
Owens, Christopher D.
通讯作者：
Owens, Christopher D.
影响因子：
6.5
作者：
BRAVERMAN, IM;KEH, A;JACOBSON, BS
通讯作者：
JACOBSON, BS