RANTES (regulated on activation, normal T cell expressed and secreted) is a chemokine implicated in atherosclerosis. Increasing evidence supports the involvement of inflammation in the initiation and progression of atherosclerosis. Chemotactic cytokines or chemokines are small heparin-binding proteins that play a critical role in the inflammatory process by directing the migration of circulating leukocytes to sites of inflammation or injury. They are classified into 4 major groups, according to the arrangement of the conserved cysteine (C) residues in the mature proteins. CC chemokines, which have the first 2 conserved cysteine residues adjacent to each other, constitute the largest family of chemokines. They tend to attract mononuclear cells and are found at sites of chronic inflammation.
CCL5 or RANTES (regulated on activation, normal T-cell expressed and secreted) is a CC chemokine that is stored in the alpha granules of platelets and that can be rapidly released after platelet activation. After release from activated platelets, it can subsequently be deposited on inflamed or atherosclerotic endothelium and has been shown to mediate transmigration and shear-resistant arrest of monocytes onto activated endothelium.
In addition, RANTES is highly expressed within atheroma.
For these reasons, RANTES has been implicated in the genesis of atherosclerosis. Despite this, however, data regarding the significance of plasma RANTES levels in coronary artery disease (CAD) have been sparse and somewhat conflicting. On the one hand, RANTES levels in patients with acute coronary syndromes have been demonstrated to be elevated, whereas levels in stable CAD have been shown to be downregulated. In addition, gene polymorphisms that would be expected to result in reduced levels of RANTES have been shown to be associated with adverse cardiac events in a stable but high-risk population. These observations raise the possibility that RANTES levels may have divergent implications in stable versus unstable CAD patients. To date, there have been no studies which have specifically looked at the prognostic value of baseline plasma RANTES levels in patients with known or suspected CAD. This is in contrast to other chemokines, such as IL-8 and MCP-1, which have also been associated with atherosclerosis and whose levels have been demonstrated to be prognostically significant.
Resources:
Cavusoglu E, Eng C, Chopra V, Clark LT, Pinsky DJ, Marmur JD. Low plasma RANTES levels are an independent predictor of cardiac mortality in patients referred for coronary angiography. Arterioscler Thromb Vasc Biol. 2007 Apr;27(4):929-35. doi: 10.1161/01.ATV.0000258789.21585.76. Epub 2007 Jan 25. PMID: 17255538.
Tang P, Chong L, Li X, Liu Y, Liu P, Hou C, Li R. Correlation between serum RANTES levels and the severity of Parkinson's disease. Oxid Med Cell Longev. 2014;2014:208408. doi: 10.1155/2014/208408. Epub 2014 Dec 22. PMID: 25587378; PMCID: PMC4283268.
Fonteh CN, Palestine AG, Wagner BD, Patnaik JL, Mathias MT, Manoharan N, Mandava N, Baldermann R, De Carlo T, Lynch AM; University of Colorado Retina Research Group. RANTES (CCL5) in Patients With Geographic Atrophy Age-Related Macular Degeneration. Transl Vis Sci Technol. 2023 Jan 3;12(1):19. doi: 10.1167/tvst.12.1.19. PMID: 36633873; PMCID: PMC9840441.
A low RANTES level signifies different things depending on the context in which it is measured:
→ In the context of cardiac health: A low plasma RANTES level has been associated with adverse outcomes in patients with coronary artery disease (CAD). RANTES (CCL5) is a chemokine that plays a critical role in the inflammatory process and is implicated in the genesis of atherosclerosis, the condition responsible for the narrowing and hardening of arteries. In a study of patients referred for coronary angiography, it was found that low baseline plasma RANTES levels were an independent predictor of cardiac mortality at 24 months. The study showed that patients with stable CAD had downregulated RANTES levels, which could be relevant in assessing the risk of adverse cardiac events.
→ In the context of age-related macular degeneration (AMD): RANTES levels have also been studied in patients with AMD. In a study of patients with geographic atrophy (GA), an advanced form of AMD, it was found that RANTES levels were significantly lower in patients with GA compared to control subjects. This finding is consistent with previous studies that also showed lower levels of RANTES in patients with intermediate AMD. Identifying systemic and retinal biomarkers like RANTES could aid in the early detection and potential treatment options for AMD.
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Elevated RANTES levels refers to an increased level of the chemokine called "Regulated upon Activation, Normal T cell Expressed and Secreted" (RANTES) in the body. Chemokines are small signaling proteins that play a crucial role in immune responses by attracting immune cells to sites of inflammation, infection, or injury. RANTES, specifically, is involved in the recruitment of immune cells, particularly T cells, to these sites.
An elevated level of RANTES could indicate an ongoing immune response or inflammation in the body. This could be due to various factors, such as:
→ Infections,
→ Autoimmune diseases,
→ Allergic reactions,
→ Tissue damage,
→ or other inflammatory conditions.
→ HIV [L]
→ ALS [L]
→ Breast cancer [L]
→ Hashimoto’s thyroiditis [L]
→ Graves’ disease [L]
→ Metabolic syndrome [L]
→ Acute coronary syndromes
Monitoring the levels of RANTES and other chemokines can provide valuable information to healthcare professionals about the nature and severity of an immune response or inflammatory process.
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CCL3 (MIP-1alpha), CCL4 (MIP-1beta), CCL5 (RANTES), Gamma interferon (IFN-gamma), Granulocyte and Monocyte CSF (GM-CSF), Interleukin-10 (IL-10), Interleukin-13 (IL-13), Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-6 (IL-6), Interleukin-8 (IL-8 o CXCL8), Ligando CD40 (sCD40L), Tumor necrosis factor alpha (TNF-alpha), Vascular Endothelial Growth Factor (VEGF)
