Hepatotoxicity of epidermal growth factor receptor - tyrosine kinase inhibitors (EGFR-TKIs).

Drug-induced liver injury (DILI) is one of the most frequently adverse reactions in clinical drug use, usually caused by drugs or herbal compounds. Compared with other populations, cancer patients are more prone to abnormal liver function due to primary or secondary liver malignant tumor, radiation-induced liver injury and other reasons, making potential adverse reactions from liver damage caused by anticancer drugs of particular concernduring clinical treatment process. In recent years, the application of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has changed the treatment status of a series of solid malignant tumors. Unfortunately, the increasing incidence of hepatotoxicitylimits the clinical application of EGFR-TKIs. The mechanisms of liver injury caused by EGFR-TKIs were complex. Despite more than a decade of research, other than direct damage to hepatocytes caused by inhibition of cellular DNA synthesis and resulting in hepatocyte necrosis, the rest of the specific mechanisms remain unclear, and few effective solutions are available. This review focuses on the clinical feature, incidence rates and the recent advances on the discovery of mechanism of hepatotoxicity in EGFR-TKIs, as well as rechallenge and therapeutic strategies underlying hepatotoxicity of EGFR-TKIs.

Injectable and Sprayable Fluorescent Nanoprobe for Rapid Real-Time Detection of Human Colorectal Tumors.

The development of minimally invasive surgery has greatly advanced precision tumor surgery, but sometime suffers from restricted visualization of the surgical field, especially during the removal of abdominal tumors. A 3-D inspection of tumors could be achieved by intravenously injecting tumor-selective fluorescent probes, whereas most of which are unable to instantly distinguish tumors via in situ spraying, which is urgently needed in the process of surgery in a convenient manner. In this study, this work has designed an injectable and sprayable fluorescent nanoprobe, termed Poly-g-BAT, to realize rapid tumor imaging in freshly dissected human colorectal tumors and animal models. Mechanistically, the incorporation of γ-glutamyl group facilitates the rapid internalization of Poly-g-BAT, and these internalized nanoprobes can be subsequently activated by intracellular NAD(P)H: quinone oxidoreductase-1 to release near-infrared fluorophores. As a result, Poly-g-BAT can achieve a superior tumor-to-normal ratio (TNR) up to 12.3 and enable a fast visualization (3 min after in situ spraying) of tumor boundaries in the xenograft tumor models, Apcmin/+ mice models and fresh human tumor tissues. In addition, Poly-g-BAT is capable of identifying minimal premalignant lesions via intravenous injection.

FTO ameliorates doxorubicin-induced cardiotoxicity by inhibiting ferroptosis via P53-P21/Nrf2 activation in a HuR-dependent m6A manner.

Doxorubicin (DOX)-induced cardiotoxicity seriously limits its clinical applicability, and no therapeutic interventions are available. Ferroptosis, an iron-dependent regulated cell death characterised by lipid peroxidation, plays a pivotal role in DOX-induced cardiotoxicity. N6-methyladenosine (m6A) methylation is the most frequent type of RNA modification and involved in DOX-induced ferroptosis, however, its underlying mechanism remains unclear. P21 was recently found to inhibit ferroptosis by interacting with Nrf2 and is regulated in a P53-dependent or independent manner, such as through m6A modification. In the present study, we investigated the mechanism underlying m6A modification in DOX-induced ferroptosis by focusing on P21. Our results show that fat mass and obesity-associated protein (FTO) down-regulation was associated with DOX-induced cardiotoxicity. FTO over-expression significantly improved cardiac function and cell viability in DOX-treated mouse hearts and H9C2 cells. FTO over-expression significantly inhibited DOX-induced ferroptosis, and the Fer-1 inhibition of ferroptosis significantly reduced DOX-induced cardiotoxicity. P21 was significantly upregulated by FTO and activated Nrf2, playing a crucial role in the anti-ferroptotic effect. FTO upregulated P21/Nrf2 in a P53-dependent manner by mediating the demethylation of P53 or in a P53-independent manner by mediating P21/Nrf2 directly. Human antigen R (HuR) is crucial for FTO-mediated regulation of ferroptosis and P53-P21/Nrf2. Notably, we also found that P21 inhibition in turn inhibited HuR and P53 expression, while HuR inhibition further inhibited FTO expression. RNA immunoprecipitation assay showed that HuR binds to the transcripts of FTO and itself. Collectively, FTO inhibited DOX-induced ferroptosis via P21/Nrf2 activation by mediating the m6A demethylation of P53 or P21/Nrf2 in a HuR-dependent manner and constituted a positive feedback loop with HuR and P53-P21. Our findings provide novel insight into key functional mechanisms associated with DOX-induced cardiotoxicity and elucidate a possible therapeutic approach.

Inhibiting microRNA-200a-3p attenuates pyroptosis via targeting the SIRT1/NF-κB/NLRP3 pathway in H2O2-induced HAEC.

Atherosclerosis is a chronic inflammatory disease of the arterial wall caused by many factors. Endothelial cell dysfunction is the initial factor in the development of atherosclerosis, and ROS activates the assembly of inflammasomes and induces the pyroptosis of vascular endothelial cells. Whether H2O2 induced human aortic endothelial cells (HAECs) pyroptosis and the underlying mechanisms remain unclear. This study aimed to investigate the role of microRNA-200a-3p in H2O2-induced HAECs pyroptosis. First, we found that the pyroptosis-related protein was upregulated in aortia in HFD apoE-/- mice. The in vitro study showed that the activation of NLRP3 inflammasomes and the pyroptosis in H2O2-induced HAECs, which is characterized by an increase in Lactate dehydrogenase (LDH) activity, and an increase in propidium iodide (PI)-positive cells. The expression of silent information regulator of transcription 1 (SIRT1) was also decreased in H2O2-induced HAECs, and the overexpression of SIRT1 could reverse the occurrence of pyroptosis, partly through p65 deacetylation, thereby inhibiting nuclear translocation of p65 and regulating NLRP3 expression. Further studies revealed increased miRNA-200a-3p expression in H2O2-induced HAECs and the promotion of pyroptosis, which was achieved by targeting SIRT1. Inhibition of miR-200a-3p reduced pyroptosis by promoting the expression of the downstream target gene SIRT1 and reducing the accumulation of p65 and NLRP3. Collectively, our results suggest that H2O2 can regulate NLRP3 inflammasomes through the miR-200a-3p/SIRT1/NF-κB (p65) signaling pathway and promote HAEC pyroptosis. The miR-200a-3p inhibitor can promote the expression of SIRT1 and inhibit pyroptosis, which may be important to prevent and treat atherosclerosis.

HZ-A-018, a novel inhibitor of Bruton tyrosine kinase, exerts anti-cancer activity and sensitizes 5-FU in gastric cancer cells.

Gastric cancer is the third leading cause of cancer related death worldwide. Due to the complexity and heterogeneity of gastric cancer, the development of targeted drugs is somehow limited, but is urgently needed. Since the expression of Bruton tyrosine kinase (BTK) was significantly associated with the prognosis of gastric cancer patients, we aimed to determine the anti-cancer activity of HZ-A-018, which was a novel derivative of ACP-196, in gastric cancer cells. As a result, HZ-A-018 presented a stronger anti-proliferation activity than ACP-196 via the substantial suppression of AKT/S6 pathway. In addition, HZ-A-018, but not ACP-196, exerted the synergistic effects in combined treatment with 5-FU both in vitro and in vivo, without exacerbating the adverse effects of 5-FU. Mechanismly, the combination of HZ-A-018 and 5-FU remarkably reduced the expression of RRM2, which played an essential role in proliferation and drug sensitivity in gastric cancer cells. In summary, our work demonstrated the stronger anti-cancer activity of HZ-A-018 than ACP-196 in gastric cancer cells, and revealed synergistic effects of HZ-A-018 and 5-FU combination probably through the inhibition of RRM2 via AKT/S6 pathway, thereby providing a promising therapeutic strategy in gastric cancer.

Ibrutinib-Associated Cardiotoxicity: From the Pharmaceutical to the Clinical.

Ibrutinib is the first-in-class Bruton tyrosine kinase (BTK) inhibitor that has revolutionized the treatment of B cell malignancies. Unfortunately, increased incidences of cardiotoxicity have limited its use. Despite over a decade of research, the biological mechanisms underlying ibrutinib cardiotoxicity remain unclear. In this review, we discuss the pharmacological properties of ibrutinib, the incidence and mechanisms of ibrutinib-induced cardiotoxicity, and practical management to prevent and treat this condition. We also synopsize and discuss the cardiovascular adverse effects related to other more selective BTK inhibitors, which may guide the selection of appropriate BTK inhibitors.

The role of exercise-induced myokines in promoting angiogenesis.

Ischemic diseases are a major cause of mortality or disability in the clinic. Surgical or medical treatment often has poor effect on patients with tissue and organ ischemia caused by diffuse stenoses. Promoting angiogenesis is undoubtedly an effective method to improve perfusion in ischemic tissues and organs. Although many animal or clinical studies tried to use stem cell transplantation, gene therapy, or cytokines to promote angiogenesis, these methods could not be widely applied in the clinic due to their inconsistent experimental results. However, exercise rehabilitation has been written into many authoritative guidelines in the treatment of ischemic diseases. The function of exercise in promoting angiogenesis relies on the regulation of blood glucose and lipids, as well as cytokines that secreted by skeletal muscle, which are termed as myokines, during exercise. Myokines, such as interleukin-6 (IL-6), chemokine ligand (CXCL) family proteins, irisin, follistatin-like protein 1 (FSTL1), and insulin-like growth factor-1 (IGF-1), have been found to be closely related to the expression and function of angiogenesis-related factors and angiogenesis in both animal and clinical experiments, suggesting that myokines may become a new molecular target to promote angiogenesis and treat ischemic diseases. The aim of this review is to show current research progress regarding the mechanism how exercise and exercise-induced myokines promote angiogenesis. In addition, the limitation and prospect of researches on the roles of exercise-induced myokines in angiogenesis are also discussed. We hope this review could provide theoretical basis for the future mechanism studies and the development of new strategies for treating ischemic diseases.

Inhibition of TRIM32 by ibr-7 treatment sensitizes pancreatic cancer cells to gemcitabine via mTOR/p70S6K pathway.

Pancreatic cancer is one of the most notorious diseases for being asymptomatic at early stage and high mortality rate thereafter. However, either chemotherapy or targeted therapy has rarely achieved success in recent clinical trials for pancreatic cancer. Novel therapeutic regimens or agents are urgently in need. Ibr-7 is a novel derivative of ibrutinib, displaying superior antitumour activity in pancreatic cancer cells than ibrutinib. In vitro studies showed that ibr-7 greatly inhibited the proliferation of BxPC-3, SW1990, CFPAC-1 and AsPC-1 cells via the induction of mitochondrial-mediated apoptosis and substantial suppression of mTOR/p70S6K pathway. Moreover, ibr-7 was able to sensitize pancreatic cancer cells to gemcitabine through the efficient repression of TRIM32, which was positively correlated with the proliferation and invasiveness of pancreatic cancer cells. Additionally, knockdown of TRIM32 diminished mTOR/p70S6K activity in pancreatic cancer cells, indicating a positive feedback loop between TRIM32 and mTOR/p70S6K pathway. To conclude, this work preliminarily explored the role of TRIM32 in the malignant properties of pancreatic cancer cells and evaluated the possibility of targeting TRIM32 to enhance effectiveness of gemcitabine, thereby providing a novel therapeutic target for pancreatic cancer.

The Role of Ferroptosis in Cardiovascular Disease and Its Therapeutic Significance.

Cardiovascular diseases (CVDs) are the leading cause of deaths worldwide with regulated cell death playing an important role in cardiac pathophysiology. However, the classical mode of cell death cannot fully explain the occurrence and development of heart disease. In recent years, much research has been performed on ferroptosis, a new type of cell death that causes cell damage and contributes to the development of atherosclerosis, myocardial infarction, heart failure, and other diseases. In this review, we discuss the role of different organelles in ferroptosis and also focus on the relationship between autophagy and ferroptosis. Additionally, we describe the specific mechanism by which ferroptosis contributes to the development of CVD. Finally, we summarize the current research on ferroptosis-related pathway inhibitors and the applications of clinically beneficial cardiovascular drugs.

Role of GTPase-Dependent Mitochondrial Dynamins in Heart Diseases.

Heart function maintenance requires a large amount of energy, which is supplied by the mitochondria. In addition to providing energy to cardiomyocytes, mitochondria also play an important role in maintaining cell function and homeostasis. Although adult cardiomyocyte mitochondria appear as independent, low-static organelles, morphological changes have been observed in cardiomyocyte mitochondria under stress or pathological conditions. Indeed, cardiac mitochondrial fission and fusion are involved in the occurrence and development of heart diseases. As mitochondrial fission and fusion are primarily regulated by mitochondrial dynamins in a GTPase-dependent manner, GTPase-dependent mitochondrial fusion (MFN1, MFN2, and OPA1) and fission (DRP1) proteins, which are abundant in the adult heart, can also be regulated in heart diseases. In fact, these dynamic proteins have been shown to play important roles in specific diseases, including ischemia-reperfusion injury, heart failure, and metabolic cardiomyopathy. This article reviews the role of GTPase-dependent mitochondrial fusion and fission protein-mediated mitochondrial dynamics in the occurrence and development of heart diseases.

Crosstalk between extracellular vesicles and autophagy in cardiovascular pathophysiology.

Extracellular vesicles are composed of loaded soluble substances and lipid bilayers; these include apoptotic bodies, exosomes, and microvesicles. Extracellular vesicles, as carriers of biological information between cells, have been recognized for their role in the diagnosis and treatment of cardiovascular diseases. The biogenesis of extracellular vesicles is closely related to autophagy. Moreover, extracellular vesicles further affect autophagy levels in target cells through their transmitted contents. Autophagy is a catabolic cell process that maintains cell homeostasis by eliminating misfolded proteins and damaged organelles. Existing studies have revealed that extracellular vesicles and autophagy share molecular mechanisms with notable crosstalk, including, perspectives such as amphisomes and "secretory autophagy." In this review, we first introduce the biogenesis of extracellular vesicles and the classic views of autophagy before moving onto the crosstalk between extracellular vesicles and autophagy. Finally, we discuss the research progress of extracellular vesicles and autophagy in cardiovascular pathophysiology.

Apoptosis, autophagy and atherosclerosis: Relationships and the role of Hsp27.

Atherosclerosis is a multifactorial chronic inflammatory disease of the arterial wall, and an important pathological basis of coronary heart disease. Endothelial cells, vascular smooth muscle cells, and macrophages play important roles in the development of atherosclerosis. Of note, apoptosis and autophagy, two types of programmed cell death, influence the development and progression of atherosclerosis via the modulation of such cells. The small heat shock protein Hsp27 is a multifunctional protein induced by various stress factors and has a protective effect on cells. A large number of studies have demonstrated that Hsp27 plays an important role in regulating apoptosis. Recently, some studies have suggested that Hsp27 also participates in the autophagic process. Moreover, Hsp27 is closely related to the occurrence and development of atherosclerosis. Here, we summarize the molecular mechanisms of apoptosis and autophagy and discuss their effects on endothelial cells, vascular smooth muscle cells, and macrophages in the context of atherosclerotic procession. We further explore the involvement of Hsp27 in apoptosis, autophagy, and atherosclerosis. We speculate that Hsp27 may exert its anti-atherosclerotic role via the regulation of apoptosis and autophagy; this may provide the basis for the development of new approaches for the prevention and treatment of atherosclerosis.

The Ibr-7 derivative of ibrutinib radiosensitizes pancreatic cancer cells by downregulating p-EGFR.

BACKGROUND: Radiotherapy is one of the main treatments for pancreatic cancer, but radiation resistance limits its clinical application. As a result, novel therapeutic agents to improve radiosensitivity are urgently needed. This study aimed to investigate the effect of Ibr-7 (a derivative of ibrutinib) on the radiosensitivity of human pancreatic cancer cells. METHODS: The effect of Ibr-7 on pancreatic cancer cell proliferation was detected by CCK-8 assays. Radiosensitivity was assessed by clonogenic formation assays. Cell cycle and cell apoptosis were analysed by flow cytometry. DNA damage was evaluated by immunofluorescence analysis. The expression levels of PARP, Cleaved caspase 3, p-EGFR and EGFR were determined by western blot. RESULTS: Ibr-7 showed an anti-proliferative effect on PANC-1 and Capan2 cells in a dose- and time-dependent manner. Ibr-7 (2 µmol/L) enhanced the effect of radiation on PANC-1 and Capan2 cells. Further findings showed that this combination enhanced G2/M phase arrest and increased cell apoptosis. Additional molecular mechanism studies revealed that the expression of p-EGFR was decreased by Ibr-7 alone or in combination with radiation. Overexpression of p-EGFR reversed the cell apoptosis induced by Ibr-7 combined with radiation. Moreover, the expression of γ-H2AX was significantly decreased in the Ibr-7 plus radiation group. CONCLUSIONS: Our study indicated the potential application of Ibr-7 as a highly effective radiosensitizer for the treatment of pancreatic cancer cells.

Expression level and diagnostic value of exosomal NEAT1/miR-204/MMP-9 in acute ST-segment elevation myocardial infarction.

Acute myocardium infarction (AMI) is one of the main causes of cardiovascular death, and timely intervention and diagnosis are essential. Owing to the irreversible apoptosis and death of myocardial cells, which ultimately causes heart failure, the problem of myocardial repair after myocardial infarction needs to be urgently addressed. Exosomes can act as messengers between cells, delivering large amounts of proteins, RNA, and lipids to receptor cells, and regulating target cell functions. Studies have shown that exosomes can repair infarcted myocardium. We aimed to investigate the relationship between long non-coding RNA NEAT1 in serum exosomes of patients and AMI and its underlying mechanism. Subjects were divided into control, UA, and STEMI groups. RNA was extracted from the serum exosomes, and the expressions of lncRNA NEAT1 and miR-204 were detected by qRT-PCR. MMP-9 was detected by western blot, Spearman test was used to analyze the correlation among the three. Logistic regression and Receiver-operating characteristic curve (ROC) were used to evaluate the prediction of acute myocardial infarction. The expressions of NEAT1 and MMP-9 in serum exosomes of patients with acute ST-segment elevation myocardial infarction were up-regulated and positively correlated, miR-204 expression was down-regulated, there were no correlations between miR-204 with NEAT1, or MMP-9. Exosomal NEAT1, miR-204, and MMP-9 displayed potent biomarkers for diagnosis of acute ST-segment elevation myocardial infarction.

GEO Data Sets Analysis Identifies COX-2 and Its Related Micro RNAs as Biomarkers for Non-Ischemic Heart Failure.

Heart failure (HF) is a heterogeneous clinical syndrome with a variety of causes, risk factors, and pathology. Clinically, only brain natriuretic peptide (BNP) or its precursor N-terminus proBNP (NTproBNP) has been validated for HF diagnosis, but they are also affected by other conditions, such as female gender, renal disease, and acute coronary syndromes, and false low levels in the setting of obesity or flash pulmonary edema. In addition, there is no one biomarker which could encompass all heart failure phenotypes. Advances in bioinformatics have provided us with large databases that characterize the complex genetic and epigenetic changes associated with human diseases. The use of data mining strategies on public access databases to identify previously unknown disease markers is an innovative approach to identify potential biomarkers or even new therapeutic targets in complex diseases such as heart failure (HF). In this study, we analyzed the genomic and transcription data of HF peripheral blood mononuclear cell (PBMC) samples obtained from the Gene Expression Omnibus data sets using Omicsbean online database (http://www.omicsbean.cn/) and found that the prostaglandin-endoperoxide synthase 2 (PTGS2), also named as cyclooxygenase-2 (COX-2), as well as its related micro RNAs including miR-1297 and miR-4649-3p might be used as potential biomarkers for non-ischemic heart failure. Our result showed that plasma COX-2 and miR-4649-3p were significantly up-regulated, whereas the plasma miR-1297 was significantly decreased, and miR-4649-3p displayed high predictive power for non-ischemic heart failure.

Role of Mitophagy in Cardiovascular Disease.

Cardiovascular disease is the leading cause of mortality worldwide, and mitochondrial dysfunction is the primary contributor to these disorders. Recent studies have elaborated on selective autophagy-mitophagy, which eliminates damaged and dysfunctional mitochondria, stabilizes mitochondrial structure and function, and maintains cell survival and growth. Numerous recent studies have reported that mitophagy plays an important role in the pathogenesis of various cardiovascular diseases. This review summarizes the mechanisms underlying mitophagy and advancements in studies on the role of mitophagy in cardiovascular disease.

MicroRNA-103 Protects Coronary Artery Endothelial Cells against H2O2-Induced Oxidative Stress via BNIP3-Mediated End-Stage Autophagy and Antipyroptosis Pathways.

Endothelial cell damage caused by oxidative stress is widely considered to be a triggering event in atherosclerosis (AS). However, the specific effect elicited by autophagy in endothelial cells undergoing oxidative stress remains controversial, especially during end-stage autophagy. The inhibition of end-stage autophagy has been reported to increase cell pyroptosis and contribute to endothelial damage. Several studies have shown that microRNA-103 is involved in end-stage autophagy; however, its specific mechanism of action is not yet characterized. In this study, we addressed the regulatory role of miR-103 in autophagy during oxidative stress of endothelial cells. Hydrogen peroxide (H2O2) treatment was used as an in vitro model of oxidative stress. MTS and ROS levels were measured to evaluate cell activity. qRT-PCR was used to detect the expression of miR-103. Autophagy was examined using western blot, immunofluorescence staining, and electron microscopy, while western blot analysis detected pyroptosis-related proteins. Results show that miR-103 expression decreased under oxidative stress. Further, miR-103 repressed transcription of Bcl-2/adenovirus E1B 19 kDa interacting protein (BNIP3). The oxidative stress caused by H2O2 caused cell damage from 2 hours (P < 0.05) and increased the level of intracellular reactive oxygen species (P < 0.05); at the same time, the damage could be further aggravated by the stimulation of bafA1 (P < 0.05). Under the stimulation of H2O2, the expression of miR-103 decreased (P < 0.05). However, high expression of miR-103 could reduce the accumulation of LC3II and P62 (P < 0.05) by inhibiting the downstream target gene Bcl-2/adenovirus E1B 19 kDa interacting protein (BNIP3), thus reducing the occurrence of cell pyroptosis (P < 0.05). This process could be blocked by end-stage autophagy inhibitor bafA1 (P < 0.05), which further indicated that miR-103 affected cell injury by autophagy. On the contrary, the low expression of miR-103 promoted the accumulation of autophagy protein and increased the occurrence of pyroptosis (P < 0.05). In conclusion, inhibition of miR-103 restrained end-stage of autophagy by regulating BNIP3, thus changing the occurrence of cell pyroptosis.

Hyperglycemia decreases anti-cancer efficiency of Adriamycin via AMPK pathway

The authors and journal apologise for an error in the above paper, which appeared in volume 25 part 11, pages 955­966. The error relates to the artwork of Fig. 5 on page 963, in which the blots given in panel E were mistakenly replicated in panel F.

A novel derivative of valepotriate inhibits the PI3K/AKT pathway and causes Noxa-dependent apoptosis in human pancreatic cancer cells.

Natural compound valepotriate exhibits inhibitory activity against a number of cancers, but the effect of valepotriate against pancreatic cancer is unclear, and the structure-activity relationship of valepotriate has not been characterized. In this study, we performed a structure-based similarity search and found 16 hit compounds. Among the 16 hits, (1S,6S,7R)-6-(acetyloxy)-1-[(3-methylbutanoyl)oxy]-4a,5,6,7a-tetrahydro-1H-spiro[cyclopenta[c]pyran-7,2'-oxiran]-4-ylmethyl 3-methylbutanoate (denoted as Amcp) exhibited superior anticancer activity against human pancreatic cancer BxPC-3 and SW1990 cells. The anti-proliferation activity of Amcp was validated in human pancreatic cancer BxPC-3 and SW1990 cells in vitro. Amcp more effectively induced apoptosis in BxPC-3 and SW1990 cells than gemcitabine. At a concentration of 15 µM, Amcp significantly suppressed the PI3K/AKT pathway and disrupted the mitochondrial membrane equilibrium through modulation of Noxa and Mcl-1 balance in both cell lines. Meanwhile, knockdown of Noxa substantially attenuated Amcp-induced reduction of cell viability and anti-apoptotic protein Mcl-1 level in BxPC-3 cells. In addition, Amcp showed synergistic anticancer effects when combined with gemcitabine in BxPC-3 cells. To conclude, this work not only suggests that Amcp possesses a dual-inhibitory activity towards PI3K/AKT pathway and Mcl-1, but also enlightens further development of bioactive valepotriate derivatives.

Long Non-Coding RNAs Link Oxidized Low-Density Lipoprotein With the Inflammatory Response of Macrophages in Atherogenesis.

Atherosclerosis is characterized as a chronic inflammatory response to cholesterol deposition in arteries. Low-density lipoprotein (LDL), especially the oxidized form (ox-LDL), plays a crucial role in the occurrence and development of atherosclerosis by inducing endothelial cell (EC) dysfunction, attracting monocyte-derived macrophages, and promoting chronic inflammation. However, the mechanisms linking cholesterol accumulation with inflammation in macrophage foam cells are poorly understood. Long non-coding RNAs (lncRNAs) are a group of non-protein-coding RNAs longer than 200 nucleotides and are found to regulate the progress of atherosclerosis. Recently, many lncRNAs interfering with cholesterol deposition or inflammation were identified, which might help elucidate their underlying molecular mechanism or be used as novel therapeutic targets. In this review, we summarize and highlight the role of lncRNAs linking cholesterol (mainly ox-LDL) accumulation with inflammation in macrophages during the process of atherosclerosis.