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Carboxyamidotriazole (CAI), originally developed as a non-cytotoxic anti-cancer drug, was shown to have anti-inflammatory activity according to recent studies in a number of animal models of inflammation. However, its mechanism of action has not been characterized. Therefore, the present study was performed to identify the anti-inflammatory action of CAI in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and to identify the signal transduction pathways involved. The in vitro results revealed that CAI had no direct effect on the activity of cyclooxygenase (COX), suggesting a different anti-inflammatory mechanism compared with that of COX-inhibiting non-steroidal anti-inflammatory drugs. Further investigation in RAW264.7 macrophages revealed that CAI decreased the production of nitric oxide via decreasing the LPS-stimulated expression of inducible nitric oxide synthase, and downregulated both mRNA and protein expression levels of the cytokines tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. CAI also significantly reduced the increased DNA-binding activity of nuclear factor (NF)-κB induced by LPS stimulation. With respect to the mechanisms involved on NF-κB activity, CAI exhibited suppression of the phosphorylation and degradation of the inhibitor of nuclear factor-κBα (IκB), and decreased the phosphorylation levels of the p65 subunit and its subsequent nuclear translocation. In addition, CAI significantly decreased the phosphorylated forms of p38, JNK and ERK, which were increased following LPS stimulation, while the total expression levels of p38, JNK and ERK remained unaltered. The results in the present study indicate that CAI alleviates the inflammatory responses of RAW 264.7 macrophages in response to LPS stimulation via attenuating the activation of NF-κB and MAPK signaling pathways and decreasing the levels of pro-inflammatory mediators. This offers a novel perspective for understanding the anti-inflammatory mechanism of CAI and suggests its potential use as a therapeutic treatment in inflammatory diseases with excessive macrophage activation. [ABSTRACT FROM AUTHOR]

• Expression of CCAT1 and SIRT1 decreased, whereas microRNA-155 was increased in the in vitro model of LPS induced AKI. • CCAT1 restoration and microRNA-155 inhibition exhibited anti-inflammation and pro-survival actions in renal epithelial cells. • SIRT1 knockdown abolished the protective effects of CCAT1 overexpression and microRNA-155 inhibition. • CCAT1 sponged microRNA-155 to regulate the expression of SIRT1. Acute kidney injury (AKI) is characterized by excessive inflammatory response and apoptosis in tubular epithelial cells. Recent studies suggested that long non-coding RNAs colon cancer-associated transcript-1 (CCAT-1) and microRNA-155 (miR-155) might regulate cell death and inflammation. We aimed to explore the role of CCAT-1/miRNA-155 axis in the AKI. LPS was applied to establish in vitro and in vivo models of AKI using HK2 cells and pcDNA-CCAT1 transgenic mice, respectively. Gene overexpression or knockdown were performed through plasmids transfection. Apoptosis were determined by qRT-PCR, western blotting (Fas, FasL, Caspase-3), AnnexinV/PI staining and TUNEL assay. Cytokines were assessed by ELISA. Interaction of CCAT1/miR-155 and miR-155/SIRT1 were detected by dual-luciferase reporter assay. RNA immunoprecipitation (RIP) was also performed to determine CCAT1/miR-155 interaction. Pathological changes of AKI were evaluated using H&E staining, blood urine nitrogen (BUN) and serum creatinine (Cr) detection kits. The degree of renal fibrosis was determined by Masson trichrome stain. LPS administration reduced CCAT1 and SIRT1 expression, but increased miR-155 levels in tubular epithelial cells in vitro. Luciferase assay demonstrated that miR-155 might bind to and regulate CCAT1 and SIRT1. RIP further confirmed the direct interaction of CCAT1 and miR-155. Restoration of CCAT1 attenuated LPS induced inflammation and apoptosis through sequestering miR-155. The anti-inflammation and pro-survival effects of CCAT1 overexpression and miR-155 inhibition were abolished by SIRT1 knockdown, as indicated by the expression of cytokine and apoptotic markers, as well as H&E, BUN and Cr detection. Dysregulated CCAT1/miR-155/SIRT1 pathway regulated disease progression in a murine model of LPS-induced AKI, and NF-κB pathway involved in. CCAT1 restoration sequestered miR-155, leading to upregulation of SIRT1 and alleviated LPS induced renal tubular epithelial cell damage in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Ischemic stroke is an acute cerebrovascular disease due to poor blood flow to the brain. Nevertheless, there is still no effective therapy for it and the pathology contributing to ischemic stroke is not fully understood. Histone Deacetylase 9 (HDAC9) is a class IIa chromatin-modifying enzyme. HDAC9 gene region is a leading risk locus for large artery atherosclerotic stroke. However, the mechanisms linking HDAC9 to ischemic remain elusive. In the study, we attempted to explore HDAC9-associated inflammatory response using the wild type (WT) and HDAC9-knockout (KO) mice with brain ischemic injury. The results indicated that WT mice with ischemia brain exhibited higher expression levels of HDAC9. HDAC9 depletion resulted in a decreased infarct volume and an improved neurological function in mice after ischemic reperfusion (I/R) injury. I/R injury markedly enhanced GFAP and Iba-1 expressions in cortex and HDAC9 knockout significantly reversed this up-regulation. Loss of HDAC9 inhibited the release of inducible NO-synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and IL-18 in cortex, hippocampus and hypothalamus of mice with I/R injury, which occurred at the transcription levels. Furthermore, the inhibitory actions of HDAC9 deficiency were associated with the down-regulation of phosphorylated-IκBα, phosphorylated-nuclear factor-kappa B (NF-κB), and p-mitogen-activated protein kinases (MAPKs), including phosphorylated-p38, phosphorylated-extracellular signal-regulated kinase 1/2 (ERK1/2), and phosphorylated- c -Jun N-terminal kinase (JNK). Importantly, the in vitro study indicated that HDAC9 inhibition-reduced inflammation and activation of IκBα/NF-κB were restored by promoting MAPKs activity in LPS-stimulated cells. Our findings suggest that HDAC9 inhibition showed neuroprotective effects on ischemic stroke by restraining inflammation, which might help develop new and effective strategies for the therapeutic interventions in ischemic stroke. [ABSTRACT FROM AUTHOR]

Objective: The study aims to determine the association between neutrophil to lymphocyte ratio (NLR) and depression and severity.Methods: We conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES). The Patient Health Questionnaire (PHQ-9) was administered to assess depression and its severity. NLR was calculated as a neutrophil count-to-lymphocyte count ratio.Results: The study included 22,207 adults (mean age, 44.43 years; women, 51.05%), and 1671 (6.54%) reported depression. The association between NLR and depression was not significant (odds ratio [OR], 1.06, 95% confidence interval [CI], 0.98 to 1.15, p = 0.12) after fully adjusting the covariates, and similar results (Q1 reference Vs Q2: OR, 0.87, 95%CI, 0.70 to 1.07 Vs Q3: OR, 0.99, 95%CI, 0.80 to 1.21 Vs Q4: OR, 1.08, 95%CI, 0.86 to 1.35, p for trend 0.21) when NLR as a categorical variable. After controlling for all confounding variables, a U-shaped relationship between NLR and depression severity was observed, and the inflection point was 1.78. Subgroup analyses showed a significant association among Mexican American/other Hispanic (OR, 1.13, 95%CI, 1.00 to 1.28, p = 0.04), non-Hispanic blacks (OR, 1.18, 95%CI, 1.07 to 1.32, p = 0.002), the subjects with poverty income ratio above four (OR, 1.24, 95%CI, 1.00 to 1.53, p = 0.048) between NLR and depression. The results from the sensitivity analyses remained stable.Conclusion: The association between NLR and depression is not general across depressed populations among US adults. This association may be specific to subgroups. The relationship between NLR and depression severity is non-linear. [ABSTRACT FROM AUTHOR]

• Atherosclerosis is a chronic inflammatory disease characterized by the development of lipid-rich plaques; • Oral infection induces atherosclerosis through local and systemic inflammatory responses; • Oral infection promotes the formation of macrophage-derived foam cells and affects lipid levels. Oral infections are common among individuals of all ages and can activate local and systemic inflammation. The inflammatory response plays an important role in atherosclerosis. An increasing number of studies have reported an association between oral pathogen infection and atherosclerotic coronary heart disease. For instance, epidemiological studies support the positive correlation between oral infections and atherosclerosis. The presence of oral pathogens in human atherosclerotic plaques has been detected by multiple methods, and oral infections promote atherosclerosis in animal experiments. Various mechanisms are involved in oral infections, thereby promoting atherosclerosis. First, oral infections can trigger the local and systemic inflammatory response, causing vascular endothelial damage. Oral-derived pathogens that enter atherosclerotic plaque can activate macrophages and cause an intra-plaque inflammatory response. Second, oral infections can promote intra-plaque macrophage cholesterol accumulation and foam cell formation. Third, oral infections can regulate plasma lipid levels, thereby increasing atherogenic lipid low-density lipoprotein and triglyceride levels. Although atherosclerosis caused by oral infections is currently studied, the precise mechanism remains to be further explored. The rise of gut microbiota research also makes the relationship between oral microbiota and disease, especially the relationship with coronary heart disease, worthy of attention and in-depth research. [ABSTRACT FROM AUTHOR]

Proprotein convertase subtilisin/kexin 9 (PCSK9) is the ninth member of the secretory serine protease family. It binds to low‐density lipoprotein receptor (LDLR) for endocytosis and lysosome degradation in the liver, resulting in an increasing in circulating LDL‐cholesterol (LDL‐c) level. Since a PCSK9 induced increase in plasma LDL‐c contributes to atherosclerosis, PCSK9 inhibition has become a new strategy in preventing and treating atherosclerosis. However, in addition to the effect of PCSK9 on elevating blood LDL‐c levels, accumulating evidence shows that PCSK9 plays an important role in inflammation, likely representing another major mechanism for PCSK9 to promote atherosclerosis. In this review, we discuss the association of PCSK9 and inflammation, and highlight the specific effects of PCSK9 on different vascular cellular components involved in the atherosclerotic inflammation. We also discuss the clinical evidence for the association between PCSK9 and inflammation in atherosclerotic cardiovascular disease. A better understanding of the direct association of PCSK9 with atherosclerotic inflammation might help establish a new role for PCSK9 in vascular biology and identify a novel molecular mechanism for PCSK9 therapy. In this review, we discuss the association of proprotein convertase subtilisin/kexin 9 (PCSK9) and inflammation, and highlight the specific effects of PCSK9 on different vascular cellular components involved in the atherosclerotic inflammation. We also discuss the clinical evidence for the association between PCSK9 and inflammation in atherosclerotic cardiovascular disease. A better understanding of the direct association of PCSK9 with atherosclerotic inflammation might help establish a new role for PCSK9 in vascular biology and identify a novel molecular mechanism for PCSK9 therapy. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a risk factor for abnormal heart development, but the molecular mechanism remains obscure. Histone deacetylase 11 (HDAC11), the most recently identified histone deacetylase, is the sole member of class IV HDACs. However, its role in diabetic cardiac injury is still poorly understood. In the present study, we attempted to explore the effects of HDAC11 on fructose (Fru)-induced cardiac injury using the wild type (HDAC11 +/+ ) and knockout (HDAC11 −/− ) mice. The results indicated that HDAC11 was significantly expressed in human and mouse diabetic heart failure (DHF) hearts. HDAC11 −/− reduced the body weight, inguinal fat-pad mass, and elevated blood pressure in Fru-fed mice. Compared to HDAC11 +/+ /Fru group, cardiac function was significantly improved in HDAC11 −/− /Fru mice. HDAC11 −/− /Fru mice exhibited reduced cardiac triacylglycerol (TG), total cholesterol (TC) and free fatty acid (FFA) levels, along with decreased mRNA levels of lipid synthesis-, lipid storage- and lipid oxidation-associated genes. In addition, HDAC11 −/− attenuated apoptosis, oxidative stress and inflammation in the heart of Fru-fed mice, as evidenced by the reduced cleavage of Caspase-3, nicotinamide adenine dinucleotide phosphate (NADPH), and xanthine oxidase (XOD) activity, enhanced superoxide dismutase (SOD) activity, as well as the decreased interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels, which was accompanied with down-regulated p-NF-κB. The results above were verified in Fru-treated primary cardiomyocytes isolated from HDAC11 +/+ or HDAC11 −/− mice. Intriguingly, suppressing the expressions of anti-oxidants using zinc protoporphyrin (ZnPP) or siNrf-2 siRNA markedly abolished the results that HDAC11 suppression-induced reduction of apoptosis, reactive oxygen species (ROS) production, inflammation, as well as the improvement of dyslipidemia in Fru-incubated primary cardiomyocytes. Thus, ROS production was responsible for HDAC11-modulated diabetic heart injury. These findings suggested that suppressing HDAC11 has therapeutic potential for treating diabetes mellitus-associated cardiac injury. [ABSTRACT FROM AUTHOR]

Ischemia/reperfusion (IR) injury causes damage in aerobically metabolizing organs or tissues, which is an essential injury mechanism in various clinical settings. SRY-related high mobility group-Box gene 9 (SOX9) is a transcription factor of the SRY family, modulating various cellular processes, including fibrosis formation and tumor growth. However, the effects of SOX9 on hepatic IR injury have not been explored. In the present study, a hepatic IR injury model was established, supported by a significant histological alteration with high Suzuki scores, and a remarkable up-regulation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Importantly, we found that SOX9 was over-expressed in liver of mice after IR operation. Suppressing SOX9 markedly reduced inflammatory response, as evidenced by the reduced mRNA expressions of tumor necrosis factor α (TNF-α), interleukin (IL)-6 and IL-1β and inactivation of inhibitor of κBα (IκBα)/nuclear factor (NF)-κB pathway. In addition, SOX9 suppression alleviated apoptosis in liver of mice after IR injury, as supported by the reduced number of terminal deoxyribonucleotidyl transferse (TdT)-mediated biotin-16-dUTP nick-end labelling (TUNEL)-staining cells and decreased expression of Caspase-3 in liver tissue sections. The role of SOX9 in accelerating hepatic IR injury was further confirmed in primary hepatocytes under hypoxiaand reoxygenation (HR) treatment by enhancing inflammatory response and apoptosis. Of note, we found that transforming growth factor (TGF)-β1 was highly induced in liver of mice after IR injury. HR treatment also stimulated TGF-β1 expressions in vitro. Significantly, SOX9 over-expression-induced inflammation and apoptosis were obviously reduced by pirfenidone (Pirf), TGF-β1 inhibitor. In contrast, TGF-β1 exposure to cells further enhanced inflammation and apoptosis in HR-operated cells either with SOX9 knockdown or over-expression. Therefore, we identified a novel SOX9-dependent pathway that contributed to hepatic IR injury through enhancing inflammation and apoptosis by activating TGF-β1. [ABSTRACT FROM AUTHOR]

Atherosclerosis is characterized by chronic inflammation and lipid accumulation in arterial walls, resulting in several vascular events. Proprotein convertase subtilisin kexin 9 (PCSK9), a serine protease, has a pivotal role in the degradation of hepatic low-density lipoprotein receptor (LDLR). It can increase plasma concentrations of low-density lipoprotein cholesterol and affect lipid metabolism. Recently, PCSK9 has been found to accelerate atherosclerosis via mechanisms apart from that involving the degradation of LDLR, with an emerging role in regulating the inflammatory response in atherosclerosis. Apolipoprotein E receptor 2 (apoER2), one of the LDLR family members expressed in macrophages, can bind to its ligand apolipoprotein E (apoE), exhibiting an anti-inflammatory role in atherosclerosis. Evidence suggests that apoER2 is a target of PCSK9. This review aims to discuss PCSK9 as a potential regulator of apoE/apoER2 against inflammation in atherosclerosis. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a complex clinical syndrome caused by various cardiovascular diseases. Its main pathogenesis includes cardiomyocyte loss, myocardial energy metabolism disorder, and activation of cardiac inflammation. Due to the clinically unsatisfactory treatment of heart failure, different mechanisms need to be explored to provide new targets for the treatment of this disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a gene mainly related to familial hypercholesterolemia, was discovered in 2003. Aside from regulating lipid metabolism, PCSK9 may be involved in other biological processes such as apoptosis, autophagy, pyroptosis, inflammation, and tumor immunity and related to diabetes and neurodegenerative diseases. Recently, clinical data have shown that the circulating PCSK9 level is significantly increased in patients with heart failure, and it is related to the prognosis for heart failure. Furthermore, in animal models and patients with myocardial infarction, PCSK9 in the infarct margin area was also found to be significantly increased, which further suggested that PCSK9 might be closely related to heart failure. However, the specific mechanism of how PCSK9 participates in heart failure remains to be further explored. The purpose of this review is to summarize the potential mechanism of PCSK9's involvement in heart failure, thereby providing a new treatment strategy for heart failure. [Display omitted] • HF needs new treatment strategies to ameliorate its present situation. • HF's pathogenesis involved cell death, energy metabolism, inflammation etc. • PCSK9 contributes to the pathogenesis of HF and may be new target for therapy. • Several PCSK9 inhibitors have been marketed and worked in cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background and aims Proprotein convertase subtilisin/kexin 9 (PCSK9) has emerged as a popular target in the development of new cholesterol-lowering drugs and therapeutic interventions for atherosclerosis. PCSK9 could accelerate atherosclerosis through mechanisms beyond the degradation of the hepatic low-density lipoprotein receptor. Several clinical studies suggested that PCSK9 is involved in atherosclerotic inflammation. Accordingly, this study aimed to explore the role of PCSK9 in vascular inflammation that promotes atherosclerotic progression. Methods We examined whether PCSK9 silencing via transduction with the lentivirus-mediated PCSK9 shRNA (LV-PCSK9 shRNA) vector affects the formation of vascular lesions in hyperlipidemia-induced atherosclerosis in apolipoprotein E knockout (apoE KO) mice. In vitro , the effects of PCSK9 on oxLDL-induced macrophages inflammation were investigate using LV-PCSK9 and LV-PCSK9 shRNA for PCSK9 overexpression and PCSK9 silencing. Results Immunohistochemical analysis showed that PCSK9 expression increased within atherosclerotic plaques in apoE KO mice. These in vivo results showed that the LV-PCSK9 shRNA group of mice developed less aortic atherosclerotic plaques compared with the control group. These lesions also had the reduced number of macrophages and decreased expression of vascular inflammation regulators, such as tumor necrosis factor-α, interleukin 1 beta, monocyte chemoattractant protein-1, toll-like receptor 4 and nuclear factor kappa B (NF-κB). We further showed that PCSK9 overexpression in macrophages in vitro increased the secretion of oxLDL-induced proinflammatory cytokines. PCSK9 overexpression upregulated TLR4 expression and increased p-IκBα levels, IkBα degradation, and NF-κB nuclear translocation in macrophages, but PCSK9 knockdown had the opposite effects in oxLDL-treated macrophages. Conclusions PCSK9 gene interference could suppress atherosclerosis directly through decreasing vascular inflammation and inhibiting the TLR4/NF-κB signaling pathway without affecting plasma cholesterol level in high-fat diet-fed apoE KO mice. PCSK9 may be an inflammatory mediator in the pathogenesis of atherosclerosis. [ABSTRACT FROM AUTHOR]

MicroRNAs are a group of endogenously small non-coding RNA molecules that downregulate gene expression at the post-transcriptional level through binding to the 3′UTR of target mRNAs. Recent findings have revealed a key role for microRNAs in the pathophysiological processes of atherosclerosis. As a complex disease, atherosclerosis is influenced by a combination of multiple genes and environmental factors. Both of them play a role in atherogenesis by affecting different types of cells (such as endothelial cell, vascular smooth muscle cell and monocyte/macrophage) function. MicroRNAs control the senescence and dysfunction of endothelial cells, proliferation and migration of vascular smooth muscle cells, and macrophage-driven cytokine production and polarization. By these effects, microRNAs can influence the processes of atherosclerosis and may represent new molecular targets for therapy. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are the leading cause of death and morbidity worldwide. Atherosclerotic cardiovascular disease (ASCVD) is affected by both environmental and genetic factors. Microenvironmental disorders of the human gut flora are associated with a variety of health problems, not only gastrointestinal diseases, such as inflammatory bowel disease, but also extralintestinal organs. Hydrogen sulfide (H 2 S) is the third gas signaling molecule other than nitric oxide and carbon monoxide. In the cardiovascular system, H 2 S plays important roles in the regulation of blood pressure, angiogenesis, smooth muscle cell proliferation and apoptosis, anti-oxidative stress, cardiac functions. This review is aiming to explore the potential role of gut microbiota in the development of atherosclerosis through hydrogen sulfide production as a novel therapeutic direction for atherosclerosis. [ABSTRACT FROM AUTHOR]

Atherosclerosis is an arterial disease associated with inflammation. Hence, the discovery of novel therapeutic agents for suppressing inflammatory responses is urgent and vital for the treatment of atherosclerosis in cardiovascular diseases. The total saponins of Aralia elata (Miq.) Seem. (TAS) are the main components extracted from the Chinese traditional herb Longya Aralia chinensis L., a folk medicine used in Asian countries for treating numerous diseases, enhancing energy and boosting immunity. However, the protective effects of TAS against inflammation-triggered vascular endothelial dysfunction, a critical early event during the course of atherosclerosis, and the potential mechanisms of this protection have been not demonstrated. Accordingly, the aim of this study was to investigate the anti-inflammatory and anti-apoptotic effects and the protective mechanisms of TAS, and show how TAS ameliorates human umbilical vein endothelial cell (HUVEC) damage caused by tumour necrosis factor-α (TNF-α). The results indicated that TAS exerted cytoprotective effects by inhibiting TNF-α-triggered HUVEC apoptosis, mitochondrial membrane potential depolarisation, and the regulation of inflammatory factors (IL-6, MCP-1, and VCAM-1) while suppressing NF-κB transcription. Furthermore, this phenomenon was related to activation of the phosphoinositide 3-kinase (PI3K)/Akt signalling pathway. Blocking the Akt pathway with LY294002, a PI3K inhibitor, reversed the cytoprotective effect of TAS against TNF-α-induced endothelial cell death. Moreover, LY294002 partially abolished the effects of TAS on the upregulation of the Bcl-2 family of proteins and the downregulation of Bax protein expression. In conclusion, the results of our study suggest that TAS suppresses the inflammation and apoptosis of HUVECs induced by TNF-α and that PI3K/Akt signalling plays a key role in promoting cell survival and anti-inflammatory reactions during this process. [ABSTRACT FROM AUTHOR]

Inflammation is a major contributing factor to the progression of atherosclerosis. Ginsenoside Rb1 (Rb1), an active saponin of Panax notoginseng, has been found to exert beneficial effects on inflammation and oxidative stress. This study investigated the ability of Rb1 to inhibit the formation of atherosclerotic plaques and the potential mechanisms. In this study, the effects of Rb1 on the development of atherosclerosis were investigated in ApoE-/- deficient mice fed with a western diet. Mice were intragastrically administrated with Rb1 (10 mg/kg) for 8 weeks. This study is that ginsenoside Rb1 exerted an inhibitory effect on early atherosclerosis in ApoE-/- mice via decreasing body weight and food intake daily, upregulating the lipid levels of serum plasma, including those of TC, TG and LDL-C and HDL-C and reducing the atherosclerotic plaque area, suppressing inflammatory cytokines (levels of IL-1β, IL-6 and TNF-α) in the serum of ApoE-/- mice, changing the expression levels of BCL-2, BAX, cleaved caspase-3 and cleaved caspase-9 and weakening apoptosis associated with anti-inflammatory activity. Hence, all these effects against atherosclerosis were tightly associated with regulation of necrosis or apoptosis associated with anti-inflammatory activity. Additionally, the results found that ginsenoside Rb1 increased autophagy flux to inhibit apoptosis via acceleration of autophagy by promoting transformation of LC3 from type I to type II in high-fat diet-induced atherosclerosis in ApoE-/- mice. This finding, along with those of the previous study, provides evidence that Rb1 promotes the process of autophagy to protect against atherosclerosis via regulating BCL-2 family-related apoptosis. These results indicate that Rb1 exhibits therapeutic effects in atherosclerosis by reversing the imbalance between apoptosis and autophagy. [ABSTRACT FROM AUTHOR]