[Anti-inflammatory effect of high-density lipoprotein on the cardiovascular system of hyperlipidemic mice].

Introduction: LDLr-/- mice are spontaneously hyperlipidemic and resistant to the development of neointimal lesions.

Objectives: This study aimed to determine the factor that prevents the inflammatory process and neointimal lesions and insulin resistance in LDLr-/- mice.

Methods: Three groups of 3-month-old male mice were used: wild-type mice (WT group); LDLr-/- mice fed a standard diet (S group); and LDLr-/- mice fed a high-fat diet (HF group). After 15 days, blood was collected for analysis of plasma lipids, glucose and insulin. The HOMA index was calculated to determine insulin resistance. The heart and aorta were removed for histological study. Histological sections of the heart were processed immunohistochemically with anti-CD40L antibodies to evaluate the inflammatory process. Histological sections of the aorta were stained with hematoxylin/eosin and picrosirius red to assess morphological and morphometric alterations.

Results: The S mice were resistant to the inflammatory process, as shown by low immunoreactivity to CD40L, with high plasma HDL levels, and did not develop insulin resistance, even with moderate hyperlipidemia compared to WT. The HF mice showed severe hyperlipidemia, increased cardiac immunoreactivity to CD40L, pronounced morphological changes in the aortic wall and insulin resistance, associated with a decrease in plasma HDL levels, compared to S. This severe hyperlipidemia in the HF mice can be considered the major metabolic factor inducing oxidative stress in the cardiovascular system, increasing the lipid peroxidation of HDL and hence its removal by the liver, with consequent lowering of plasma HDL levels.

Conclusion: High HDL plasma levels are a protective factor against the development of cardiovascular inflammation and insulin resistance in LDLr-/- mice, preventing the development of neointimal lesions.