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外源性生长激素加重易损性心外膜冠状动脉照射后的动脉粥样硬化。

Exogenous Growth Hormone Exacerbates Post-Irradiation Atherosclerosis in Susceptible Epicardial Coronary Arteries.

机构信息

Tulane National Primate Research Center, Covington, Louisiana, USA.

Tulane University School of Medicine, New Orleans, Louisiana, USA.

出版信息

Toxicol Pathol. 2024 Aug;52(6):308-318. doi: 10.1177/01926233241277454. Epub 2024 Sep 10.

Abstract

Cardiac exposure to ionizing radiation can damage both the microvasculature and coronary arteries, as well as increase the long-term risk of heart disease, myocardial fibrosis, and conduction abnormalities. Therapeutic agents capable of promoting recovery from radiation injury to the heart are limited. Growth hormone is linked to improved cardiac function following injury. Here, we leveraged a cynomolgus macaque model to determine the long-term outcomes of recombinant human growth hormone (rhGH) therapy on the heart following low-dose ionizing radiation. Macaques were exposed to 2 Gy radiation, treated with rhGH for one month, and assessed after 2 years. Overall, plasma lipid profile, cardiac function, and coronary artery disease were similar between rhGH and placebo treated animals. However, a subgroup of rhGH-treated animals exhibited more extensive atherosclerotic plaques in the coronary arteries. Together, these findings indicate that transient human growth hormone therapy subsequent to a single low dose of ionizing radiation involving the heart does not result in long-term changes to plasma cholesterol but may promote exacerbated coronary artery disease in a subset of individuals.

摘要

心脏暴露于电离辐射会损害微血管和冠状动脉,并增加患心脏病、心肌纤维化和传导异常的长期风险。能够促进心脏辐射损伤恢复的治疗药物有限。生长激素与损伤后心脏功能的改善有关。在这里,我们利用食蟹猴模型来确定低剂量电离辐射后重组人生长激素(rhGH)治疗对心脏的长期影响。恒河猴接受 2 Gy 辐射,rhGH 治疗一个月,并在 2 年后进行评估。总体而言,rhGH 和安慰剂治疗动物的血浆脂质谱、心功能和冠状动脉疾病相似。然而,rhGH 治疗动物亚组的冠状动脉中存在更广泛的动脉粥样硬化斑块。总之,这些发现表明,单次低剂量涉及心脏的电离辐射后进行短暂的人类生长激素治疗不会导致血浆胆固醇的长期变化,但可能会使一部分人出现更严重的冠状动脉疾病。

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