Metabolic adaptations of cells at the vascular-immune interface during atherosclerosis

Bonacina, Fabrizia; Dalt, L. Da; Catapano, A.L.; Norata, Giuseppe Danilo

doi:10.1016/j.mam.2020.100918

Cited by 22 publications

(10 citation statements)

References 141 publications

(139 reference statements)

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“…AS represents a systemic chronic inflammatory disease involving activated innate immune responses ( Gencer et al, 2021 ). AS lesion is filled with immune cells that may orchestrate and trigger inflammatory response ( Bonacina et al, 2021 ). Increasing evidence suggests the inherent immune diversity in AS plaques ( Shen et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Characterization of an Aging-Based Diagnostic Gene Signature and Molecular Subtypes With Diverse Immune Infiltrations in Atherosclerosis

Zhao

Zheng

et al. 2022

Front. Mol. Biosci.

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Objective: Advancing age is a major risk factor of atherosclerosis (AS). Nevertheless, the mechanism underlying this phenomenon remains indistinct. Herein, this study conducted a comprehensive analysis of the biological implications of aging-related genes in AS.Methods: Gene expression profiles of AS and non-AS samples were curated from the GEO project. Differential expression analysis was adopted for screening AS-specific aging-related genes. LASSO regression analysis was presented for constructing a diagnostic model, and the discriminatory capacity was evaluated with ROC curves. Through consensus clustering analysis, aging-based molecular subtypes were conducted. Immune levels were estimated based on the expression of HLAs, immune checkpoints, and immune cell infiltrations. Key genes were then identified via WGCNA. The effects of CEBPB knockdown on macrophage polarization were examined with western blotting and ELISA. Furthermore, macrophages were exposed to 100 mg/L ox-LDL for 48 h to induce macrophage foam cells. After silencing CEBPB, markers of cholesterol uptake, esterification and hydrolysis, and efflux were detected with western blotting.Results: This study identified 28 AS-specific aging-related genes. The aging-related gene signature was developed, which could accurately diagnose AS in both the GSE20129 (AUC = 0.898) and GSE43292 (AUC = 0.685) datasets. Based on the expression profiling of AS-specific aging-related genes, two molecular subtypes were clustered, and with diverse immune infiltration features. The molecular subtype–relevant genes were obtained with WGCNA, which were markedly associated with immune activation. Silencing CEBPB triggered anti-inflammatory M2-like polarization and suppressed foam cell formation.Conclusion: Our findings suggest the critical implications of aging-related genes in diagnosing AS and modulating immune infiltrations.

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Section: Discussionmentioning

confidence: 99%

Characterization of an Aging-Based Diagnostic Gene Signature and Molecular Subtypes With Diverse Immune Infiltrations in Atherosclerosis

Zhao

Zheng

et al. 2022

Front. Mol. Biosci.

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“…Interestingly, cultured ECs with VSMCs also changed ECs morphology, increased EC gene expression of tissue factor [ 29 ], VEGF [ 27 ], adhesion molecules [ 30 ], growth-related oncogene-α and monocyte chemotactic protein-1 [ 31 ]. Moreover, paracrine factors released from EC could also be regulators of VSMCs metabolic processes that has been described important in the context of immunometabolism response in the vascular remodeling disease such as atherosclerosis [ 32 ]. Some soluble factors from EC have the capacities to change the low density lipoprotein metabolism of VSMCs [ 33 ] or reduce cholesteryl ester hydrolysis as compared to solo-cultured VSMCs [ 34 ].…”

Section: Ec–vsmc Communicationmentioning

confidence: 99%

Cellular Crosstalk between Endothelial and Smooth Muscle Cells in Vascular Wall Remodeling

Méndez‐Barbero

Gutiérrez-Muñoz

Blanco-Colio

2021

IJMS

104

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Pathological vascular wall remodeling refers to the structural and functional changes of the vessel wall that occur in response to injury that eventually leads to cardiovascular disease (CVD). Vessel wall are composed of two major primary cells types, endothelial cells (EC) and vascular smooth muscle cells (VSMCs). The physiological communications between these two cell types (EC–VSMCs) are crucial in the development of the vasculature and in the homeostasis of mature vessels. Moreover, aberrant EC–VSMCs communication has been associated to the promotor of various disease states including vascular wall remodeling. Paracrine regulations by bioactive molecules, communication via direct contact (junctions) or information transfer via extracellular vesicles or extracellular matrix are main crosstalk mechanisms. Identification of the nature of this EC–VSMCs crosstalk may offer strategies to develop new insights for prevention and treatment of disease that curse with vascular remodeling. Here, we will review the molecular mechanisms underlying the interplay between EC and VSMCs. Additionally, we highlight the potential applicable methodologies of the co-culture systems to identify cellular and molecular mechanisms involved in pathological vascular wall remodeling, opening questions about the future research directions.

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“…Investigating the effects (if any) of prescribed medications on these biomarkers in PCOS women would yield a more accurate assessment of cardiometabolic risk including aspects of cell activation at the vascular immune interface [ 22 ].…”

Section: Emerging Cardiometabolic Risk Biomarkersmentioning

confidence: 99%

Pharmacological Approaches to Controlling Cardiometabolic Risk in Women with PCOS

Cignarella

Mioni

Sabbadin

et al. 2020

IJMS

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Polycystic ovary syndrome (PCOS) is characterized by elevated androgen production and subclinical changes in cardiovascular and metabolic risk markers. Total cholesterol, high-density lipoprotein (HDL) cholesterol, fasting glucose, and fasting insulin appear to increase specifically in PCOS compared with fertile women. PCOS also confers an increased risk of cardiometabolic disease in later life. Novel biomarkers such as serum’s cholesterol efflux capacity and blood-derived macrophage activation profile may assist in more accurately defining the cardiometabolic risk profile in these women. Aldosterone antagonists, androgen receptor antagonists, 5α-reductase inhibitors, and synthetic progestogens are used to reduce hyperandrogenism. Because increased insulin secretion enhances ovarian androgen production, short-term treatment with metformin and other hypoglycemic agents results in significant weight loss, favorable metabolic changes, and testosterone reduction. The naturally occurring inositols display insulin-sensitizing effects and may be also used in this context because of their safety profile. Combined oral contraceptives represent the drug of choice for correction of androgen-related symptoms. Overall, PCOS management remains focused on specific targets including assessment and treatment of cardiometabolic risk, according to disease phenotypes. While new options are adding to established therapeutic approaches, a sometimes difficult balance between efficacy and safety of available medications has to be found in individual women.

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Metabolic adaptations of cells at the vascular-immune interface during atherosclerosis

Cited by 22 publications

References 141 publications

Characterization of an Aging-Based Diagnostic Gene Signature and Molecular Subtypes With Diverse Immune Infiltrations in Atherosclerosis

Characterization of an Aging-Based Diagnostic Gene Signature and Molecular Subtypes With Diverse Immune Infiltrations in Atherosclerosis

Cellular Crosstalk between Endothelial and Smooth Muscle Cells in Vascular Wall Remodeling

Pharmacological Approaches to Controlling Cardiometabolic Risk in Women with PCOS

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