Section Vascular Biology and Inflammation, School of Cardiovascular Medicine & Sciences, British Heart Foundation Centre for Research Excellence, Faculty of Life Sciences & Medicine, King's College London, London, UK.
Eur J Clin Invest. 2021 Sep;51(9):e13579. doi: 10.1111/eci.13579. Epub 2021 May 3.
Cardiorenal syndrome in diabetes is characterised by alterations of the cardiovascular system paralleled by kidney disease with progressive renal function decline. In diabetes, chronic metabolic and haemodynamic perturbations drive endothelial dysfunction, inflammation, oxidative stress and progressive tissue fibrosis which, in turn, lead to heart and renal anatomo-functional damage. In physiology, vascular growth factors have been implicated in vascular homeostasis; their imbalance, in disease setting such as diabetes, leads to vascular dysfunction and cardiorenal damage.
To define the role of vascular growth factors and angiopoietins in cardiorenal syndrome.
We will focus on the two most studied vascular growth factors, vascular endothelial growth factor (VEGF) and angiopoietins (Angpt). The balance and crosstalk between these growth factors are important in organ development and in the maintenance of a healthy vasculature, heart and kidney. The observed alterations in expression/function of these vascular growth factors, as seen in diabetes, are a protective response against external perturbations.
The chronic insults driving diabetes-mediated cardiorenal damage results in a paradoxical situation, whereby the vascular growth factors imbalance becomes a mechanism of disease. Studies have explored the possibility of modulating the expression/action of vascular growth factors to improve disease outcome. Experimental work has been conducted in animals and has been gradually translated in humans.
Difficulties have been encountered especially when considering the magnitude, timing and duration of interventions targeting a selective vascular growth factor. Targeting VEGF in cardiovascular disease has been challenging, while modulation of the Angpt system seems more promising.
Future studies will establish the translatability of therapies targeting vascular growth factors for heart and kidney disease in patients with diabetes.
糖尿病性心肾综合征的特征是心血管系统改变，同时伴有肾功能进行性下降的肾脏疾病。在糖尿病中，慢性代谢和血液动力学改变会导致内皮功能障碍、炎症、氧化应激和进行性组织纤维化，进而导致心脏和肾脏的解剖和功能损伤。在生理学中，血管生长因子被认为与血管稳态有关；在糖尿病等疾病状态下，它们的失衡会导致血管功能障碍和心肾损伤。
定义血管生长因子和血管生成素在心肾综合征中的作用。
我们将重点关注两种研究最多的血管生长因子，血管内皮生长因子（VEGF）和血管生成素（Angpt）。这些生长因子之间的平衡和相互作用对于器官发育和维持健康的血管、心脏和肾脏非常重要。在糖尿病中观察到的这些血管生长因子表达/功能的改变是对外部干扰的一种保护反应。
导致糖尿病介导的心肾损伤的慢性损伤会导致一种矛盾的情况，即血管生长因子的失衡成为疾病的一种机制。研究已经探索了调节血管生长因子的表达/作用以改善疾病结局的可能性。实验工作已经在动物中进行，并逐渐在人类中进行转化。
在考虑针对特定血管生长因子的干预的幅度、时间和持续时间时，遇到了困难。针对心血管疾病中的 VEGF 进行靶向治疗具有挑战性，而调节 Angpt 系统似乎更有前途。
未来的研究将确定针对糖尿病患者心脏和肾脏疾病的血管生长因子靶向治疗的转化能力。
