Vascular growth factors as potential new treatment in cardiorenal syndrome in diabetes

TY - JOUR

T1 - Vascular growth factors as potential new treatment in cardiorenal syndrome in diabetes

AU - Ricciardi, Carlo Alberto

AU - Gnudi, Luigi

N1 - Funding Information: CAR is supported by a Clinical research fellowship from Kidney Research UK (Kidney Research UK, TF_001_20171120). Publisher Copyright: © 2021 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/9

Y1 - 2021/9

N2 - Background: 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. Aims: To define the role of vascular growth factors and angiopoietins in cardiorenal syndrome. Material and Methods: 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. Results: 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. Discussion: 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. Conclusion: Future studies will establish the translatability of therapies targeting vascular growth factors for heart and kidney disease in patients with diabetes.

AB - Background: 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. Aims: To define the role of vascular growth factors and angiopoietins in cardiorenal syndrome. Material and Methods: 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. Results: 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. Discussion: 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. Conclusion: Future studies will establish the translatability of therapies targeting vascular growth factors for heart and kidney disease in patients with diabetes.

KW - cardiorenal syndrome

KW - endothelial dysfunction

KW - fibrosis

KW - inflammation

KW - vascular growth factors

UR - http://www.scopus.com/inward/record.url?scp=85105027905&partnerID=8YFLogxK

U2 - 10.1111/eci.13579

DO - 10.1111/eci.13579

M3 - Review article

AN - SCOPUS:85105027905

SN - 0014-2972

VL - 51

JO - European Journal of Clinical Investigation

JF - European Journal of Clinical Investigation

IS - 9

M1 - e13579

ER -