Abstract
Endothelial dysfunction (ED) is a key factor for the development of cardiovascular diseases. Due to its chronic, life-threatening nature, ED only can be studied experimentally in animal models. Therefore, this work was aimed to characterize a murine model of ED induced by a daily intraperitoneal administration of angiotensin II (AGII) for 10 weeks. Oxidative stress, inflammation, vascular remodeling, hypertension, and damage to various target organs were evaluated in treated animals. The results indicated that a chronic intraperitoneal administration of AGII increases the production of systemic soluble VCAM, ROS and ICAM-1 expression, and the production of TNFα, IL1β, IL17A, IL4, TGFβ, and IL10 in the kidney, as well as blood pressure levels; it also promotes vascular remodeling and induces non-alcoholic fatty liver disease, glomerulosclerosis, and proliferative retinopathy. Therefore, the model herein proposed can be a representative model for ED; additionally, it is easy to implement, safe, rapid, and inexpensive.
Highlights
The endothelium is a single-cell lining that covers the internal surface of blood vessels, cardiac valves, and various body cavities[1,2]
The endothelium produces both agonistic and antagonistic molecules that help keeping h omeostasis[2]. When this balance is disrupted, it favors vasculature vasoconstriction, leukocyte adherence, platelet activation, mitogenesis, prooxidation, thrombosis, impaired coagulation, vascular inflammation, and atherosclerosis. This altered condition is known as endothelial dysfunction (ED), since it reduces the capacity of endothelium to maintain homeostasis and leads to the development of vascular diseases like systemic arterial hypertension (SAHT), renal dysfunction, and cerebrovascular diseases, which are the main causes of morbidity and mortality w orldwide[1,3,4,5]
The model performance was confirmed by increased levels of the soluble adhesion molecule, sVCAM, a parameter known to increase during this p athology[15]
Summary
The endothelium is a single-cell lining that covers the internal surface of blood vessels, cardiac valves, and various body cavities[1,2] It acts as a gatekeeper, sensing and responding to stimuli (physical or chemical, like changes in blood flow or pressure, inflammatory signals, or the levels of circulating hormones) and activating vasoactive systems that help maintaining vasomotor balance and homeostasis in vascular tissues. The model proposed is based on 1) an acute hypertension model developed by Jiménez-Ferrer et al.[13]; in that model, the authors established that an i.v. dose of 1 μg/kg of AGII (Sigma) increased SBP by 20% and DBP by about 60% with respect to normal values (120/70 mmHg); and 2) a work performed on isolated, endothelial cell-denuded aorta rings in an organ bath. The authors proposed this model, in which subject mice showed hypertension, but a complete ED condition, as evinced by prooxidant and proinflammatory activity, vascular remodeling, and damage to target organs
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