Aortic morphological changes in Metabolic Syndrome: Therapeutic contrast with atorvastatin and sleeve gastrectomy

Abstract

The atherosclerotic pathogenesis of Metabolic Syndrome (MS) comes from oxidative stress (OS) and systemic endothelial inflammation. Reactive oxygen species (ROS) damage membrane proteins, DNA, and lipids, resulting in mitochondrial dysfunction and increased ROS production, causing a vicious circle that keeps an inflammatory state and OS in the aortic wall. Pharmacological treatment with atorvastatin and surgical intervention by sleeve gastrectomy (SG) are therapies used to reduce the rate of cardiovascular events in MS. The purpose of the present study was to analyze and compare the aortic morphological changes after treatment with atorvastatin and SG in an experimental model of MS.

We used 32 male rats (Wistar) divided into the following groups: Control (C)(n=8), SM(n=8), MS+atorvastatin(MS+A)(n=8) and MS+SG(MS+SG)(n =8). SM was induced by administering 10% fructose in drinking water for 60 days. Atorvastatin 10 mg was used for 45 days. SG was performed achieving a 80% of gastric restriction. Histological sections of the thoracic aorta were analyzed by light microscopy (MO) and electron microscopy (ME).

The control group showed undamaged endothelium and elastic aortic walls preserved. In MS group, we observed sectors of endothelial denudation and myxoid areas. The MS+SG group showed thickened vessel walls and myxoid areas, without significant changes. The OM of MS+A showed regression of the lesion at the endothelial level. Mitocondrial size and shape were normal in the control group. In MS groups, we identified notable mitochondrial changes in the aortic muscularis with loss of electron density of the mitochondrial matrix and cristae disorganization. The MS+SG group showed a greater endothelial damage with vesicularization of the cytoplasm and changes in smooth muscle cells, also presenting irregular cell limits. Finally, in the MS+A group we observed a decreased swelling with reorganization of the matrix and cristae.

Endothelial dysfunction in MS is a consequence of mitochondrial changes that lead to damage in endothelium features. Pharmacological treatment with atorvastatin could reduce cardiovascular risk in MS by improving vascular damage by reversing mitochondrial alterations. However, these benefits have not been seen with surgical treatment. The study of aortic histological changes and mitochondrial architecture may lead to new treatment strategies for MS and the risk of cardiovascular events.