The role of cytokines, adhesion molecules, and toll-like receptors in atherosclerosis progression: the effect of Atorvastatin

Abstract

Inflammatory cytokines, cell adhesion molecules, and toll-like receptors (TLRs) play an important role in atherosclerosis. The aim of this study was to further evaluate the role of inflammatory cytokines, cell adhesion molecules, and toll-like receptors in atherosclerosis. Forty local breed domestic male rabbits were divided randomly into 4 groups, 10 rabbits each. Group I was the control group, group II received a high cholesterol diet, group III received the drug solvent dimethyl sulfoxide (DMSO), and group IV received Atorvastatin (3.5 mg/kg/day). Blood samples were collected at 0 times, 5 weeks, and at the end of 10 weeks. TLRs expression on monocyte was measured by flow cytometry, IL-10, IL-17, IL-1β, intracellular adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM) were measured by ELISA. In group II, a high cholesterol diet led to a statistically significant elevation of lipids profile (TC, TG, and LDL) at both 5 weeks and 10 weeks compared to the control. The expression of TLRs was also increased compared to the control (13.53±2.5 to 25.79±6.5). The intimal thickness increased from 103.46±13.85 to 248.43±11.11. IL-17 increased significantly from 3.4±0.4 to 7.7±1.00, and IL-1β increased from 1.04±0.19 to 9.66±1.4 (P 0.05) at 10 weeks. ICAM and VCAM increased from 1.7±0.16 to 8.2±0.74 and from 0.89±0.07 to 5.2±0.45, respectively. Atorvastatin significantly reduced TLRs at 10 weeks to 21.98±3.4 and intimal thickness to 191.6±15.59. IL-17, IL-1β, ICAM, and VCAM were significantly reduced by Atorvastatin. Cytokines, cellular adhesion molecules, and probably TLRs have a role in the pathogenesis of hyperlipidemia and atherosclerosis.

“How to Release or Not Release, That Is the Question.” A Review of Interleukin‐1 Cellular Release Mechanisms in Vascular Inflammation

“…There are several medications addressing this stage of intervention, statin medications being a prime example by lowering cholesterol, cholesterol species and at the same time exerting anti‐inflammatory effects through the IL‐1 receptor. 9 Beyond the receptor complex, several treatment options exist in either inhibiting or disrupting the activation of NF‐κB ( Table ), 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 which localizes to the nucleus to influence the transcription of mRNA leading to the NLRP3 inflammasome and pro‐IL‐1β production.…”

“…In atherosclerosis, many cytokines are released locally in the vessel wall such as IL‐1, IL‐18, and IL‐6, 7 with IL‐1 having been extensively investigated in animals and humans, 8 and have been shown to be reduced using the traditional lipid‐lowering medications (eg, atorvastatin). 9 Within atherosclerotic plaques, IL‐1 can be released from endothelial cells (ECs), 10 vascular smooth muscle cells (VSMCs), 11 and immune‐derived cells 12 through a stimulus dependent and cell‐type specific release process. 13 Once released, IL‐1 plays a pivotal role in atherosclerosis progression from early stages of atherogenesis 14 to the formation of complex unstable lesions.…”

The interaction between oral microbiota and gut microbiota in atherosclerosis

“…Infections enable the progression or development of AS happens by augmenting atherosclerotic alterations in vascular tissues ( 1 ). The multiple alterations encompass the increased absorption of cholesterol and modification of low-density lipoprotein (LDL) ( 19 ), the elevation of adhesion molecules and inflammatory protein expression ( 20 , 21 ), and the promotion of blood clotting. Furthermore, specific pathogens involved in AS through accelerating the conversion of macrocytes into foam cells and triggering the release of cytokines that may result in plaque instability and even rupture, thus exerting atherosclerotic effects in macrophages ( 22 , 23 ).…”

Human Immunodeficiency Virus as a Risk Factor for Cardiovascular Disease

“…The expression of the adhesion molecules VCAM-1 and ICAM-1, which mediate inflammation and promote leukocyte migration, is stimulated by HIV-Tat-1 protein and proinflammatory cytokines such as TNF-α and IL-1β [135]. Toll-like receptors activate the expression of VCAM-1 and ICAM-1 in the endothelium, a response that is strongly associated with increased intimal leukocyte accumulation, an important factor in the pathogenesis of human atherosclerosis [136]. VCAM-1 is a diagnostic biomarker of endothelial…”