Cellular Senescence and Vitamin D Deficiency Play a Role in the Pathogenesis of Obesity-Associated Subclinical Atherosclerosis: Study of the Potential Protective Role of Vitamin D Supplementation

Abstract

The exact link between obesity, vitamin D deficiency, and their relation to cellular senescence in the pathogenesis of subclinical atherosclerosis is still under debate. Therefore, the current study aims to verify the possible role of vitamin D deficiency and cellular senescence in the pathogenesis of obesity-related subclinical atherosclerosis. Moreover, it aims to investigate the possible protective role of vitamin D supplementation. Fifty-seven male albino rats were enrolled in the study and classified into four groups: negative (10) and positive control groups (10), an obese model group (24), and a vitamin-D-supplemented obese group (13). Aortic tissue samples and fasting blood samples were collected. The following biochemical investigations were performed: serum cholesterol, triglycerides, HDL-C, LDL-C, ALT, AST, CPK, CK-MB, and hs-cTnt. HOMA-IR was calculated. Moreover, serum SMP-30, 25 (OH)Vitamin D₃, and eNOS were determined by the ELISA technique. Aortic gene expression of eNOS, SMP-30, and P53 was estimated by real-time qRT-PCR. Serum 25(OH) D₃ and SMP-30 were lower in the obese group. In addition, the obese group showed higher serum lipid profile, HOMA-IR, eNOS, ALT, AST, CPK, CK-MB, and hs-cTnt than the control groups, while decreased levels were found in the vitamin-D-treated obese group. Gene expression of eNOS and SMP-30 were in accordance with their serum levels. A positive correlation was found between vitamin D level and SMP-30. In conclusion, obesity is associated with vitamin D deficiency and enhanced cellular senescence. They could play a role in the pathogenesis of obesity-associated subclinical atherosclerosis and endothelial dysfunction. Vitamin D supplements could play a protective role against such obesity-related comorbidity.

Keywords: atherosclerosis; endothelial dysfunction; obesity; senescence; vitamin D.

Figure 1

The gene expression of eNOS, SMP-30, and P53 in all studied animal groups.

Figure 2

Histological examination of the aorta of the different studied groups. (A) A section from the aorta of a control rat showing a thin wall formed of tunica intima, tunica media, and tunica adventitia. Tunica intima reveals simple squamous endothelium with underlying lamina propria. Tunica media is formed of concentrically arranged smooth muscle with parallel internal elastic membranes. Tunica adventitia shows vasa vasorum. (B) A section from the aorta of a diseased rat showing loss of endothelial cells, and thickening of tunica intima and media with protrusion of intima into the lumen. (C) A section from the aorta of a diseased rat showing apparent thickening of tunica adventitia with presence of fat cells and inflammatory cells and congested vasa vasorum. (D) A section from the aorta of treated rats showing the relative improvement of the wall, apart from some lost endothelial cells.