IntroductionAtherosclerosis can trigger various cardiovascular and cerebrovascular diseases with complex pathogenesis. Macrophage proliferation, inflammatory responses, and lipid phagocytosis, which induce foam cell formation and accumulation, are critical in the development of early atherosclerotic lesions. The role of 3-Hydroxystearic acid (C18-3OH), a recently identified gut microbiota-derived metabolite, in atherosclerosis has not yet been clarified. This study aimed to investigate the role of the ALKBH5/PAX-8/ABCA1 pathway in C18-3OH-mediated regulation of macrophage cholesterol efflux and atherosclerosis and explore novel mechanisms of ABCA1 regulation from the perspective of m6A modification.MethodsRT-qPCR and Western blotting were used to detect gene and protein expression, respectively. ChIP-Seq was used to screen PAX-8 target genes, and ChIP-qPCR was used to validate PAX-8 binding to ABCA1. The SRAMP platform was used to predict m6A modification sites in PAX-8 mRNA sequences. Methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) was used to measure m6A modification levels of PAX-8 mRNA in foam cells. UHPLC-OEMS untargeted metabolomics were used to analyze differential fatty acid metabolites in an atherosclerotic mouse model. Specific kits were used to detect serum liver function markers (aspartate transaminase, AST; alanine aminotransferase, ALT), renal function markers (serum creatinine, Scr; blood urea nitrogen, BUN), and lipid profiles (HDL-C, TG, LDL-C, TC). Aortic sinus sections were prepared, and H&E, Oil Red O, and Masson staining were used to evaluate atherosclerotic plaques.ResultsThe results demonstrated that C18-3OH promoted cholesterol efflux in foam cells and alleviated lipid accumulation by upregulating ABCA1 expression. C18-3OH inhibited ALKBH5, increased PAX-8 mRNA m6A modification and PAX-8 expression, and upregulated ABCA1 to enhance cholesterol efflux. Serum metabolomics revealed reduced C18-3OH levels in high-fat diet-fed apoE-/- atherosclerotic mice. C18-3OH suppressed aortic ALKBH5 expression, elevated m6A modification of PAX-8 mRNA, and increased PAX-8 and ABCA1 expression. Furthermore, C18-3OH improved lipid metabolism and reduced the atherosclerotic plaque area in apoE-/- mice.DiscussionThis study clarifies the impact and mechanisms of gut microbiota-derived C18-3OH on atherosclerosis progression, providing novel strategies for the precise prevention and treatment of atherosclerosis.

Macrophage cholesterol efflux, a critical step in reverse cholesterol transport, plays a pivotal role in the attenuation of atherosclerosis. Echinacoside, a natural compound with anti-inflammatory, antioxidant, and antitumor properties, has emerged as a potential therapeutic agent for atherosclerosis. However, the mechanisms underlying its anti-atherosclerotic effects remain unclear. In this study, we aimed to investigate the effects of echinacoside on lipid accumulation in macrophage-derived foam cells and on atherosclerotic progression in apoE-/- mice. Our key findings indicated that echinacoside upregulated ABCA1 expression, enhanced macrophage cholesterol efflux, and reduced lipid accumulation by modulating MDM2/PPARγ signaling. Additionally, echinacoside alleviated atherosclerotic progression in high-fat diet-fed apoE-/- mice. MDM2 overexpression with pcDNA3.1-MDM2 eliminated the effects of echinacoside on ABCA1 and PPARγ upregulation, macrophage cholesterol efflux, and lipid accumulation. In conclusion, echinacoside inhibits macrophage lipid accumulation and alleviates atherosclerotic progression via the MDM2/PPARγ/ABCA1 signaling pathway.

The renin-angiotensin system (RAS), composed mainly of renin, angiotensin, and aldosterone, is a key endocrine pathway involved in cardiovascular activity regulation. Under physiological conditions, the RAS plays a vital role in water and salt metabolism, blood pressure regulation, and electrolyte balance. Angiotensin II (Ang II) is the most important active component of the RAS, and its receptors are concentrated in vascular, pulmonary, cardiac, and renal tissues in vivo. Moreover, Ang II is closely associated with the development of vascular lesions. Ang II expression is closely associated with atherosclerosis, aortic aneurysm/dissection, ischemic stroke, hypertension, pulmonary hypertension, and type 2 diabetes mellitus. Given the significant pathophysiological role of Ang II in vascular diseases and the availability of advanced detection methods, Ang II holds promise as a reliable biomarker and therapeutic target in clinical settings. This review summarizes the mechanisms through which Ang II contributes to different vascular diseases and discusses its potential application as a biomarker for disease diagnosis.

Nuclear factor interleukin-3 (NFIL3), a proline- and acidic-residue-rich (PAR) bZIP transcription factor, is called the E4 binding protein 4 (E4BP4) as well, which is relevant to regulate the circadian rhythms and the viability of cells. More and more evidence has shown that NFIL3 is associated with different cardiovascular diseases. In recent years, it has been found that NFIL3 has significant functions in the progression of atherosclerosis (AS) via the regulation of inflammatory response, macrophage polarization, some immune cells and lipid metabolism. In this overview, we sum up the function of NFIL3 during the development of AS and offer meaningful views how to treat cardiovascular disease related to AS.

ATP-binding cassette protein A1 (ABCA1) is a key protein in the transport of intracellular cholesterol to the extracellular and plays an important role in reducing cholesterol accumulation in surrounding tissues. Bibliometric analysis refers to the cross-science of quantitative analysis of a variety of documents by mathematical and statistical methods. It combines an analysis of structural and temporal patterns in scholarly publications with a description of topic concentration and types of uncertainty. This paper analyzes the history, hotspot, and development trend of ABCA1 through bibliometrics. It will provide readers with the research status and development trend of ABCA1 and help the hot research in this field explore new research directions. After screening, the research on ABCA1 is still in a hot phase in the past 20 years. ABCA1 is emerging in previously unrelated disciplines such as cancer. There were 551 keywords and 6888 breakout citations counted by CiteSpace. The relationship between cancer and cardiovascular disease has been linked by ABCA1. This review will guide readers who are not familiar with ABCA1 research to quickly understand the development process of ABCA1 and provide researchers with a possible future research focus on ABCA1.

Vascular disease is a common problem with high mortality all over the world. Apelin-13, a key subtype of apelin, takes part in many physiological and pathological responses via regulating many target genes and target molecules or participating in many signaling pathways. More and more studies have demonstrated that apelin-13 is implicated in the onset and progression of vascular disease in recent years. It has been shown that apelin-13 could ameliorate vascular disease by inhibiting inflammation, restraining apoptosis, suppressing oxidative stress, and facilitating autophagy. In this article, we sum up the progress of apelin-13 in the occurrence and development of vascular disease and offer some insightful views about the treatment and prevention strategies of vascular disease.

The ribonucleic acid (RNA)-binding protein Cytoplasmic Polyadenylation Element Binding Protein 1 (CPEB1), a key member of the CPEB family, is essential in controlling gene expression involved in both healthy physiological and pathological processes. CPEB1 can bind to the 3'- untranslated regions (UTR) of substrate messenger ribonucleic acid (mRNA) and regulate its translation. There is increasing evidence that CPEB1 is closely related to the pathological basis of atherosclerosis. According to recent investigations, many pathological processes, including inflammation, lipid metabolism, endothelial dysfunction, angiogenesis, oxidative stress, cellular senescence, apoptosis, and insulin resistance, are regulated by CPEB1. This review considers the prevention and treatment of atherosclerotic heart disease in relation to the evolution of the physiological function of CPEB1, recent research breakthroughs, and the potential participation of CPEB1 in atherosclerosis.

Macrophage lipid accumulation indicates a pathological change in atherosclerosis. Ilexgenin A (IA), a pentacyclic triterpenoid compound, plays a role in preventing inflammation, bacterial infection, and fatty liver and induces a potential anti-atherogenic effect. However, the anti-atherosclerotic mechanism remains unclear. The present study investigated the effects of IA on lipid accumulation in macrophage-derived foam cells and atherogenesis in apoE-/- mice. Our results indicated that the expression of adenosine triphosphate-binding cassette transporter A1 (ABCA1) was up-regulated by IA, promoting cholesterol efflux and reducing lipid accumulation in macrophages, which may be regulated by the protein tyrosine phosphatase non-receptor type 2 (PTPN2)/ERK1/2 signalling pathway. IA attenuated the progression of atherosclerosis in high-fat diet-fed apoE-/- mice. PTPN2 knockdown with siRNA or treatment with an ERK1/2 agonist (Ro 67 -7476) impeded the effects of IA on ABCA1 upregulation and cholesterol efflux in macrophages. These results suggest that IA inhibits macrophage lipid accumulation and alleviates atherosclerosis progression via the PTPN2/ERK1/2 signalling pathway.

Atherosclerosis is the major pathophysiological basis of a variety of cardiovascular diseases and has been recognized as a lipid-driven chronic inflammatory disease. Gelsolin (GSN) is a member of the GSN family. The main function of GSN is to cut and seal actin filaments to regulate the cytoskeleton and participate in a variety of biological functions, such as cell movement, morphological changes, metabolism, apoptosis and phagocytosis. Recently, more and more evidences have demonstrated that GSN is Closely related to atherosclerosis, involving lipid metabolism, inflammation, cell proliferation, migration and thrombosis. This article reviews the role of GSN in atherosclerosis from inflammation, apoptosis, angiogenesis and thrombosis.

Cardiovascular diseases (CVDs) are a series of diseases induced by inflammation and lipid metabolism disorders, among others. Metabolic diseases can cause inflammation and abnormal lipid metabolism. C1q/TNF-related proteins 1 (CTRP1) is a paralog of adiponectin that belongs to the CTRP subfamily. CTRP1 is expressed and secreted in adipocytes, macrophages, cardiomyocytes, and other cells. It promotes lipid and glucose metabolism but has bidirectional effects on the regulation of inflammation. Inflammation can also inversely stimulate CTRP1 production. A vicious circle may exist between the two. This article introduces CTRP1 from the structure, expression, and different roles of CTRP1 in CVDs and metabolic diseases, to summarize the role of CTRP1 pleiotropy. Moreover, the proteins which may interact with CTRP1 are predicted through GeneCards and STRING, speculating their effects, to provide new ideas for the study of CTRP1.

Tyrosine-protein phosphatase non-receptor type 2(PTPN2), an important member of the protein tyrosine phosphatase family, can regulate various signaling pathways and biological processes by dephosphorylating receptor protein tyrosine kinases. Accumulating evidence has demonstrated that PTPN2 is involved in the occurrence and development of atherosclerotic cardiovascular disease. Recently, it has been reported that PTPN2 exerts an anti-atherosclerotic effect by regulating vascular endothelial injury, monocyte proliferation and migration, macrophage polarization, T cell polarization, autophagy, pyroptosis, and insulin resistance. In this review, we summarize the latest findings on the role of PTPN2 in the pathogenesis of atherosclerosis to provide a rationale for better future research and therapeutic interventions.

Oxidized low‑density lipoprotein (ox‑LDL) can increase the expression of adipophilin and the accumulation of intracellular lipid droplets. However, the detailed mechanisms remain to be fully elucidated. The present study aimed to investigate the mechanism underlying the effect of ox‑LDL on the expression of adipophilin and the accumulation of intracellular cholesterol esters. The results revealed that ox‑LDL increased the activation of protein kinase C α (PKCα), expression of adipophilin and acyl‑coenzymeA: cholesterol acyltransferse 1 (ACAT1) and increased accumulation of intracellular cholesterol esters. In addition, PKCα siRNA abrogated ox‑LDL‑induced adipophilin, expression of ATAC1 and accumulation of cholesterol esters. Furthermore, ox‑LDL increased the accumulation of intracellular cholesterol esters and expression of ACAT1, and this effect were reversed by transfection with adipophilin siRNA. Taken together, these results demonstrated that ox‑LDL induces the accumulation of cholesterol esters, which is mediated by the PKCα‑adipophilin‑ACAT1 pathway.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Concerns raised by Dr. Sander Kersten in PubPeer pointed out that Figs. 6.1B and 6.2B of this paper were different figures but the legends and Western blots were identical; the quantification was also seen to be different between the two figures. Shortly afterwards, the authors asked to publish a corrigendum for part B of Fig. 6.1, including images of western blots and associated bar plots. Subsequently, the journal conducted an investigation and found evidence that there had been improper manipulation and duplication of images in Fig. 2 E, 6.2 B, 5 A and and 6.2 D, as shown by the reuse of several western blot bands with approximately 180° rotation in each case. After raising the complaint with the authors, the corresponding author agreed that the paper should be retracted. The authors apologise to the readers of the journal.

Transcription factors, as the convergence points of multiple signaling pathways in eukaryotic cells, are closely involved in disease development. Pax-8, an important transcription factor belonging to the Pax family, exerts a crucial influence on the regulation of gene expression required for both physiological conditions and pathological processes. Pax-8 contributes to the pathogenesis of many human diseases, ranging from cardiovascular disease to many cancers, and therefore, it can be imagined that Pax-8 holds great therapeutic potential. In this review, we summarize the structure, distribution, function, and regulatory mechanisms of Pax-8 to provide a new research direction for Pax-8.

Recently, we read an interesting paper titled "CREB1 transcription-activated lncRNA PVT1 promotes cardiac fibrosis via miR-145/HCN1 axis" written by Tian and his colleagues [ [1] Tian C. Hu S. Yu J. et al. CREB1 transcription-activated lncRNA PVT1 promotes cardiac fibrosis via miR-145/HCN1 axis. Int. J. Cardiol. 2022; 353: 88-95 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar ]. This finding implies that PVT1 is up-regulated in cardiac fibrosis models in vivo and in vitro. Further studies showed that PVT1 contributed to cardiac fibrosis via sponging miR-145. It suggests that targeting PVT1 may be a therapeutic option for cardiovascular disease (CVD).

Atherosclerosis, the underlying pathophysiological basis of cardiovascular disease, has been recognized as a lipid-driven chronic inflammatory disease. Sterol carrier protein 2 (SCP-2) is a 13-kDa non-specific lipid-transfer protein expressed by various tissues and cells, such as liver, heart, vascular smooth muscle cells (VSMCs), and macrophages. SCP-2 has an extensive role in cardiovascular and metabolic diseases. Recently, SCP-2 was reported to promote the development of atherosclerosis by regulating lipid metabolism and peroxidation, endocannabinoid metabolism, vascular inflammation, and fatty acid metabolism. In this review, we summarized the recent advances regarding the role of SCP-2 in the pathogenesis of atherosclerosis and tried to provide a rationale for future investigation and a better understanding of the biological functions of SCP-2 in atherosclerotic cardiovascular disease.

Non-alcoholic fatty liver disease (NAFLD) is considered as the most common chronic liver disease and has become a rapidly global public health problem. Sterol carrier protein 2 (SCP-2), also called non-specific lipidtransfer protein, is predominantly expressed by the liver. SCP-2 plays a key role in intracellular lipid transport and metabolism. SCP-2 has been closely implicated in the development of NAFLD-related metabolic disorders, such as obesity, atherosclerosis, Type 2 diabetes mellitus (T2DM), and gallstones. Recent studies indicate that SCP-2 plays a beneficial role in NAFLD by regulating cholesterol-, endocannabinoid-, and fatty acid-related aspects of lipid metabolism. Hence, in this paper, we summarize the latest findings about the roles of SCP-2 in hepatic steatosis and further describe its molecular function in the pathogenesis of NAFLD.