Trained immunity in monocyte/macrophage: Novel mechanism of phytochemicals in the treatment of atherosclerotic cardiovascular disease

Abstract

Atherosclerosis (AS) is the pathology of atherosclerotic cardiovascular diseases (ASCVD), characterized by persistent chronic inflammation in the vessel wall, in which monocytes/macrophages play a key role. It has been reported that innate immune system cells can assume a persistent proinflammatory state after short stimulation with endogenous atherogenic stimuli. The pathogenesis of AS can be influenced by this persistent hyperactivation of the innate immune system, which is termed trained immunity. Trained immunity has also been implicated as a key pathological mechanism, leading to persistent chronic inflammation in AS. Trained immunity is mediated via epigenetic and metabolic reprogramming and occurs in mature innate immune cells and their bone marrow progenitors. Natural products are promising candidates for novel pharmacological agents that can be used to prevent or treat cardiovascular diseases (CVD). A variety of natural products and agents exhibiting antiatherosclerotic abilities have been reported to potentially interfere with the pharmacological targets of trained immunity. This review describes in as much detail as possible the mechanisms involved in trained immunity and how phytochemicals of this process inhibit AS by affecting trained monocytes/macrophages.

Berberine modulates cardiovascular diseases as a multitarget-mediated alkaloid with insights into its downstream signals using in silico prospective screening approaches

“…Atherosclerotic CVDs are resulted from deposition and retention of atherosclerotic plaques, monocytes adhesion and migration, and macrophage foam cells formation in the walls of coronary arteries that restrict blood flow and cause tissue hypoxia. Atherosclerotic CVDs is also characterized by a low-grade, persistent, and chronic inflammatory features ( Xie et al, 2020 , Wang et al, 2023 ). Sigma-1 receptor (SIGMAR1) is a chaperone transmembrane receptor presented at the mitochondrial-associated ER membranes.…”

“…Berberine is a natural isoquinoline alkaloid isolated from Traditional Chinese herbs such as Coptis chinensis and Berberis vulgaris . Berberine is identified as a safe and curative agent to treat diabetes, hyperlipidemia, and pathogenesis of CVDs through upregulating cellular glucose and lipids metabolism, attenuating oxidative stress generation and inflammation, and inhibiting apoptotic signals ( Younis et al, 2022 , Wang et al, 2023 ). ER stress response potentiates myocardial cells apoptosis, cardiac remodeling, and heart failure.…”

“…In ApoE -/- mice fed with HFD and HepG2 cells, the administration with berberine also improved the relative expression levels of RCT-mediated lipids metabolism genes and proteins, which enhanced the levels of hepatic LDLR, ABCA1, ABCG1, and SR-B1 and decreased the level of hepatic PCSK9 through upregulating and activating the MAPK/ ERK1/2 signaling pathway ( Ma et al, 2021 ). Berberine greatly upregulates LXRα/ABCA1-dependent cholesterol efflux signaling and reduces macrophage foam cells formation through activating AMPK/SIRT1 and autophagy signals, decreasing expression of pro-inflammatory modulators (TNFα,IL1β, IL6, and iNOS), and increasing expression of anti-inflammatory mediators (IL10) ( Wang et al, 2023 ). In the LBD pocket of LXRα nuclear receptor, berberine chloride formed diversity of interactions with active Leu:331B, Phe:257B, Met:298B, Leu:260B, Thr:302B, Arg:305B, Phe:315B, and Ala:261B key residues, which introduced as a potent LXRα regulator, upregulated RCT signaling, improved lipids homeostasis, reduced formation of the macrophage-derived foam cells, and alleviated oxidative stress generation and vascular inflammation.…”

“…These antioxidant modulators improve vascular endothelial cells dysfunction, foam cells and atherosclerotic lesions formation, pathogenesis of CVDs, and apoptosis through upregulating the cellular cholesterol uptake receptors and its efflux transporters signaling and alleviating the levels of vascular oxidative stress and pro-inflammatory modulators such as LPO, IL6, IL1β, TNFα, IFNγ, iNOS, and MCP-1 ( Ooi et al, 2018 , Wu et al, 2022 ). As proatherogenic factors, TNFα, IL6, MCP-1/CCL2, and MMP9 potentially accelerate monocytes migration and adhesion, induce endothelial cells dysfunction, accelerate foam cells formation, disturb macrophages cholesterol efflux signaling, and develop pathogenesis features of CVDs ( Huwait et al, 2021 , Wang et al, 2023 ).…”

The Nutriepigenome

“…A role in human health in the prevention of aging and age-related diseases such as diabetes, osteoporosis, cancer and cardiovascular disease has been claimed, likely due to their anti-inflammatory, antioxidant, neuroprotective, chemo-preventive agents. Many review fully covered this topic [37,38] we only mention some of them for their clear role in epigenome regulation. Vitamins C is an antioxidant capable to inhibit peroxidative processes protecting cells, DNA and protein from oxidative damage.…”