Maffei Pietro, Dassie Francesca, Wennberg Alexandra, Parolin Matteo, Vettor Roberto
Clinica Medica 3, Department of Medicine (DIMED), Padua University Hospital, Padua, Italy.
Clinica Neurologica, Department of Neurosciences (DNS), Padua University Hospital, Padua, Italy.
Front Endocrinol (Lausanne). 2019 Jul 24;10:437. doi: 10.3389/fendo.2019.00437. eCollection 2019.
Growth hormone (GH) and insulin like growth factor-1 (IGF-1) excess induce well-known deleterious effects on the cardiovascular system, especially after long-term exposition. Acromegaly, a condition of chronic GH and IGF-1 hypersecretion, is frequently associated to cardiovascular complications, although recent studies have shown a reduction in the prevalence of these comorbidities in well-controlled patients and a mortality risk similar to normal aging population. Many factors could contribute to the increased cardiovascular risk of acromegaly patients. Among these factors, the endothelium plays a key role in the pathogenesis of atherosclerotic plaques and could be considered an early marker of atherosclerosis and cardiovascular dysfunction. In this review we examined the relationship between GH/IGF-1 excess and the endothelium, from basic studies to clinical evidence. Many studies involving various arterial districts (microvascular arteries of retina, kidney and brain, and major vessels as carotid and aorta) showed that GH/IGF-1 excess promotes endothelial dysfunction via several different mechanisms. Increased endothelial proliferation, dysfunction of endothelial progenitor cells, increased oxidative stress, and compromised oxidative defenses are the main factors that are associated with endothelial dysfunction. In the general population, these alterations are associated with the development of atherosclerosis with an increased incidence of coronary artery disease and cerebrovascular complications. However, in acromegaly this is still a debated issue, despite the presence of many pro-atherogenic factors and comorbidities, such as hypertension, diabetes, sleep apnoea, and metabolic syndrome. Preclinical markers of atherosclerosis as arterial intima media thickness, pulse wave velocity and flow mediated dilation seem to be impaired in acromegaly and partly mediated by the endothelium dysfunction. In conclusion, the pathophysiology of endothelial dysfunction in the condition of GH and IGF-1 excess remains a crucial area of investigation to fully dissect the association of acromegaly with cardiovascular disease complications.
生长激素（GH）和胰岛素样生长因子-1（IGF-1）过量对心血管系统会产生众所周知的有害影响，尤其是在长期暴露之后。肢端肥大症是一种慢性GH和IGF-1分泌过多的病症，常伴有心血管并发症，尽管最近的研究表明，病情得到良好控制的患者中这些合并症的患病率有所降低，且死亡风险与正常老龄化人群相似。许多因素可能导致肢端肥大症患者心血管风险增加。在这些因素中，内皮在动脉粥样硬化斑块的发病机制中起关键作用，可被视为动脉粥样硬化和心血管功能障碍的早期标志物。在本综述中，我们研究了从基础研究到临床证据的GH/IGF-1过量与内皮之间的关系。许多涉及不同动脉区域（视网膜、肾脏和大脑的微血管动脉，以及颈动脉和主动脉等主要血管）的研究表明，GH/IGF-1过量通过几种不同机制促进内皮功能障碍。内皮细胞增殖增加、内皮祖细胞功能障碍、氧化应激增加和氧化防御受损是与内皮功能障碍相关的主要因素。在普通人群中，这些改变与动脉粥样硬化的发展相关，冠状动脉疾病和脑血管并发症的发病率增加。然而，在肢端肥大症中，尽管存在许多促动脉粥样硬化因素和合并症，如高血压、糖尿病、睡眠呼吸暂停和代谢综合征，但这仍是一个有争议的问题。动脉粥样硬化的临床前标志物，如动脉内膜中层厚度、脉搏波速度和血流介导的扩张，在肢端肥大症中似乎受损，部分由内皮功能障碍介导。总之，在GH和IGF-1过量情况下内皮功能障碍的病理生理学仍然是一个关键的研究领域，以充分剖析肢端肥大症与心血管疾病并发症之间的关联。
