New insights into ANGPLT3 in controlling lipoprotein metabolism and risk of cardiovascular diseases.

Dyslipidemia, characterized by elevation of plasma low density lipoprotein cholesterol (LDL-C), triglyceride (TG) and reduction of plasma high density lipoprotein cholesterol (HDL-C), has been verified as a causal risk factor for cardiovascular diseases (CVD), leading to a high mortality rate in general population. It is important to understand the molecular metabolism underlying dyslipidemia in order to reduce the risk and to develop effective therapeutic approaches against CVD. ANGPTL3 (human) or Angptl3 (mouse), one member of the angiopoietin-like protein (ANGPTL) family, has been identified as an important regulator of lipid metabolism by inhibiting LPL and EL activity. Results have demonstrated that inactivation of Angptl3 in mice could obviously reduce the level of TG, LDL-C and the atherosclerotic lesion size, leading to a lower risk for dyslipidemia and CVD. Additionally, in humans, carriers with homozygous LOF mutations in ANGPTL3 have lower plasma LDL-C, TG levels and lower risk of atherosclerosis compared to the non-carriers. Here, we collect the latest data and results, giving a new insight into the important role of ANGPTL3 in controlling lipoprotein metabolism. Finally, we introduce two update reports on the antisense oligonucleotide and monoclonal antibody-based inactivation of ANGPTL3 in human clinical trials, to identify that ANGPTL3 could be a novel and effective target for the treatment of dyslipidemia and CVD.

New insights into apolipoprotein A5 in controlling lipoprotein metabolism in obesity and the metabolic syndrome patients.

Apolipoprotein A5 (apoA5) has been identified to play an important role in lipid metabolism, specifically in triglyceride (TG) and TG-rich lipoproteins (TRLs) metabolism. Numerous evidence has demonstrated for an association between apoA5 and the increased risk of obesity and metabolic syndrome, but the mechanism remains to be fully elucidated. Recently, several studies verified that apoA5 could significantly reduce plasma TG level by stimulating lipoprotein lipase (LPL) activity, and the intracellular role of apoA5 has also been proved since apoA5 is associated with cytoplasmic lipid droplets (LDs) and affects intrahepatic TG accumulation. Furthermore, since adipocytes provide the largest storage depot for TG and play a crucial role in the development of obesity, we could infer that apoA5 also acts as a novel regulator to modulate TG storage in adipocytes. In this review, we focus on the association of gene and protein of apoA5 with obesity and metabolic syndrome, and provide new insights into the physiological role of apoA5 in humans, giving a potential therapeutic target for obesity and associated disorders.

MG132 Induces Expression of Monocyte Chemotactic Protein-Induced Protein 1 in Vascular Smooth Muscle Cells.

Monocyte chemoattractant protein-1 (MCP-1) has been reported to induce the expression of monocyte chemotactic protein-induced protein 1 (MCPIP1), which undergoes ubiquitination degradation. Therefore, we predict that in vascular smooth muscle (VSMCs), MCPIP1 may be induced by MCP-1 and undergo degradation, which can be inhibited by the proteasome inhibitor, MG132. Our results showed that treatment of human VSMCs with MCP-1 did not increase the expression of MCPIP1. Treatment with MG132, however, elevated MCPIP1 protein levels through stimulation of the gene transcription, but not through increasing protein stability. MCPIP1 expression induced by MG132 was inhibited by α-amanitin inhibition of gene transcription or cycloheximide inhibition of protein synthesis. Our further studies showed that MCPIP1 expression induced by MG132 was inhibited by the inhibitors of AKT and p38 kinase, suggesting a role of the AKT-p38 pathway in MG132 effects. We also found that treatment with MG132 induces apoptosis, but overexpression of MCPIP1 inhibited bromodeoxyuridine (BrdU) incorporation of human VSMCs without induction of significant apoptosis. In summary, MCPIP1 expression is induced by MG132 likely through activation of the AKT-p38 pathway. MCPIP1 inhibits SMC proliferation without induction of apoptosis. J. Cell. Physiol. 232: 122-128, 2017. © 2016 Wiley Periodicals, Inc.

The unsolved mystery of apoA-I recycling in adipocyte.

As the major storage site for triglycerides and free cholesterol, adipose tissue plays a central role in energy metabolism. ApoA-I is the main constituent of HDL and plays an important role in removal of excess cholesterol from peripheral tissues. Recently, multiple studies have shown beneficial effects of apoA-I on adipose metabolism and function. ApoA-I was reported to improve insulin sensitivity and exert anti-inflammatory, anti-obesity effect in animal studies. Interestingly, Uptake and resecretion of apoA-I by adipocytes has been detected. However, the significance of apoA-I recycling by adipocytes is still not clear. This article reviewed methods used to study cellular recycling of apoA-I and summarized the current knowledge on the mechanisms involved in apoA-I uptake by adipocytes. Since the main function of apoA-I is to mediate reverse cholesterol transport from peripheral tissues, the role of apoA-I internalization and re-secretion by adipocytes in intracellular cholesterol transport under physiological and pathological conditions were discussed. In addition, findings on the correlation between apoA-I recycling and obesity were discussed. Finally, it was proposed that during intracellular transport, apoA-I-protein complex may acquire cargoes other than lipids and deliver regulatory information when they were resecreted into the plasma. Although apoA-I recycling by adipocytes is still an unsolved mystery, it's likely that it is more than a redundant pathway especially under pathological conditions.

Myocyte Enhancer Factor 2A Regulates Hydrogen Peroxide-Induced Senescence of Vascular Smooth Muscle Cells Via microRNA-143.

Myocyte enhancer factor 2A (MEF2A) is involved in vascular smooth muscle cell (VSMC) proliferation, migration, and senescence. MicroRNA-143/145 (miR-143/145), which may be regulated by MEF2A, is known to promote cellular senescence. We hypothesized that MEF2A may promote VSMC senescence via miR-143/145. VSMC senescence was induced by hydrogen peroxide (H(2)O(2)), followed by detection using a senescence-associated ß-galactosidase staining kit. The MEF2A protein, mRNA, and miR-143/145 levels in VSMCs were detected using Western blot analysis and SYBR green real-time quantitative PCR, respectively. We further manipulated the expression levels of MEF2A and miR-143 through viral or transient transfection. VSMC proliferation and migration were determined by methylthiazolyldiphenyl-tetrazolium bromide and Millicell chamber, respectively. Both MEF2A and miR-143, but not miRNA-145, were up-regulated in senescent VSMCs. Overexpression of either MEF2A or miR-143 significantly enhanced VSMC senescence, but reduced proliferation and migration. MEF2A knockdown or miR-143 inhibitor suppressed cellular senescence and increased proliferation and migration. We further revealed AKT signaling as a potential miR-143 target, and an induction of miR-143 expression by MEF2A via KLF2. Additionally, overexpression of MEF2A and miR-143 resulted in synergistic effects on promotion of senescence, and MEF2A knockdown and miR-143 reduction by inhibitor had synergistic inhibitory effects. Finally, MEF2A barely promoted VSMC senescence when miR-143 was inhibited, and miR-143 overexpression antagonized the inhibitory effect of MEF2A knockdown on VSMC senescence. Our results revealed a link and interaction between MEF2A and miR-143 and suggested a potential mechanism for MEF2A to regulate H(2)O(2) -induced VSMC senescence.

Chinese Expert Consensus on the Clinical Diagnosis and Management of Statin Intolerance.

The clinical benefits of statins have well-established and recognized worldwide. Although statins are well-tolerated generally, however, the report of statin-related adverse event and statin intolerance are common in China, which results in insufficient use of statins and poor adherence. The main reason may be attributed to confusions or misconceptions in the clinical diagnosis and management in China, including the lack of unified definitions and diagnostic standards, broad grasp of diagnosis, and unscientific management strategies. Based on that, this consensus carefully summarized the statin-related gene polymorphism and statin usage issue among Chinese population, and comprehensively reviewed global research data on statin intolerance, referenced guidelines, and consensus literature on statin intolerance in foreign and different regions, proposes an appropriate and easy to implement statin intolerance definition as well as corresponding diagnostic criteria and management strategies for Chinese clinicians, in order to improve the clinical application of statin drugs and enhance the prevention and treatment level of atherosclerotic cardiovascular disease in China.

The role of monocyte phenotype switching in peri-procedural myocardial injury and its involvement in statin therapy.

Peri-procedural myocardial injury, which is associated with worse long-term clinical outcome, is a common complication related to inflammatory pathogenetic mechanisms. Monocytes and macrophages play key roles in the initiation and progression of atherosclerosis. Recent studies have demonstrated that monocytes in human peripheral blood are heterogeneous, including CD14+CD16- monocytes and CD14+CD16+ monocytes. Several lines of evidence suggested that CD14+CD16+ monocytes might contribute to the accelerated atherosclerosis. In view of the heightened appreciation of the heterogeneity of circulating monocytes, we hypothesized that an up-shifting subset of CD14+CD16+ monocytes might be induced by percutaneous coronary intervention (PCI), which subsequently leads to peri-procedural myocardial injury. Moreover, statins loading before PCI could exert anti-inflammatory effects partly by modulating monocyte phenotype and thus prevent peri-procedural myocardial injury.

2023 Chinese guideline for lipid management.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of Chinese guideline for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "Chinese guideline for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with cardiovascular disease (CVD) risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

2023 China Guidelines for Lipid Management.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of China guidelines for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "China Guidelines for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with CVD risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

The effects of myocyte enhancer factor 2A gene on the proliferation, migration and phenotype of vascular smooth muscle cells.

The genetic basis for the phenotypic switching of vascular smooth muscle cells (VSMCs) is unclear in atherosclerosis. Recent studies showed that the 21-base pair deletion mutation (Δ21) in myocyte enhancer factor 2A (MEF2A) gene could be an inherited marker for coronary artery disease. MEF2A mutation may affect the phenotypic switching of VSMCs. Human aortic VSMCs were used. Four groups of VSMCs transfected with green fluorescent protein plasmid (control group), MEF2A wild-type (WT) plasmid (WT group), MEF2A Δ21 plasmid (Δ21 group) or MEF2A siRNA (siRNA group) were studied. The proliferation of VSMCs was determined by methylthiazolyldiphenyl-tetrazolium bromide, and the migration of VSMCs was measured by Millicell chamber. The protein expressions of MEF2A, smooth muscle α-actin, SM22α, osteopontin and p38 mitogen-activated protein kinase signaling pathway were detected by Western blotting. MEF2A protein expression was knockdown by siRNA transfection. MEF2A protein was overexpressed in WT and Δ21 groups. Δ21 and siRNA groups obviously showed more proliferation (methylthiazolyldiphenyl-tetrazolium bromide, 0.63 vs 0.66 vs 0.31, P < 0.01) and migration (52.6 vs 58.0 vs 21.2, P < 0.01) of VSMCs as compared with the WT group. In addition, the transfection of Δ21 and siRNA could induce the down-regulation of smooth muscle α-actin and SM22α (P < 0.01) and the up-regulation of osteopontin (P < 0.01) in VSMCs. The phosphorylated p38 signaling pathway expression was significantly enhanced in the Δ21 and siRNA groups as compared with that of the WT group (P < 0.01). These results suggest that MEF2A dominant negative mutation and RNA silence could induce the phenotypic switching of VSMCs, leading to its increased proliferation and migration, and p38 mitogen-activated protein kinase signaling pathway may participate in it.

Influence of vitamin D supplementation on plasma lipid profiles: a meta-analysis of randomized controlled trials.

Observational studies have shown that low serum levels of vitamin D have been associated with an atherogenic lipid profile. However, the intervention studies gave divergent results. We conducted a meta-analysis of randomized controlled trials that evaluated the effects of vitamin D supplementation on blood lipids. A systematic literature search was conducted via MEDLINE, Cochrane library, and EMBASE for randomized controlled clinical trials assessing the effects of vitamin D supplementation on lipids. The mean change in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) from baseline was treated as a continuous variable. In all, 12 clinical trials consisting of 1346 participants were included in the analysis. The pooled estimate of effect for vitamin D supplementation on LDL-C was 3.23 mg/dl (95% confidence interval, 0.55 to 5.90 mg/dl). No statistically significant effects for vitamin D supplementation were observed for TC, HDL-C and TG (differences in means were 1.52 mg/dl (-1.42 to 4.46 mg/dl), -0.14 mg/dl (-0.99 to 0.71 mg/dl) and -1.92 mg/dl (-7.72 to 3.88 mg/dl) respectively). The lipid modulating effects of vitamin D supplementation should be further investigated though large-scale, randomized trials with adequate doses which can effectively elevated the active form of vitamin D in plasma and with proper population which has hyperlipemia as an inclusion criterion.

[Effect of liver X receptor agonist T0901317 on endothelin-1 induced murine HL-1 cardiomyocytes hypertrophy].

OBJECTIVE: To investigate the role of liver X receptors (LXRs) on endothelin-1 (ET-1) induced murine HL-1 cardiomyocytes hypertrophy. METHODS: Cultured murine HL-1 cardiomyocytes were divided into four experiment groups: (1) CONTROL GROUP:treated with DMSO; (2) T0901317 group:treated with LXRs agonist T0901317 (1 µmol/L); (3) ET-1 group:treated with ET-1 (1 nmol/L); (4) T0901317 + ET-1 group:treated with T0901317 (1 µmol/L) for 8 hours, then treated with ET-1 (1 nmol/L). Twenty-four hours later, immunofluorescent staining was performed on HL-1 cells, the surface area of HL-1 cells was analyzed with NIH Image J software, and the synthetic rate of protein in HL-1 cells was detected by (3)H-leucine incorporation. The mRNA level of atrial natriuretic peptide (ANP) and ß-myosin heavy chain (ß-MyHC) was measured by quantitative realtime PCR. The effect of T0901317 on mRNA expression of ANP was also detected after LXRs gene silencing. RESULTS: The surface area of HL-1 cells, mRNA expression of ANP and ß-MyHC, and (3)H-leucine incorporation in ET-1 group were 2.00 ± 0.29, 1.98 ± 0.47, 2.13 ± 0.39 and 1.79 ± 0.17, respectively, which were significantly higher than those of control group (1.00 ± 0.26, 1.00 ± 0.21, 1.00 ± 0.31 and 1.00 ± 0.03, respectively, all P < 0.05). Compared with ET-1 group, the surface area of HL-1 cells, mRNA expression of ANP and ß-MyHC, and (3)H-leucine incorporation were significantly decreased in T0901317 + ET-1 group (1.24 ± 0.25, 1.19 ± 0.21, 1.48 ± 0.27 and 1.15 ± 0.11, respectively, all P < 0.05). After inhibition of LXRα/ß expression in HL-1 cardiomyocytes using the specific siRNAs, the mRNA expression of ANP in T0901317 + ET-1 group was 1.78 ± 0.05, which was similar as that in ET-1 group (1.94 ± 0.17, P > 0.05). CONCLUSION: T0901317, an agonist of LXRs, could inhibit ET-1 induced cardiac hypertrophy in vitro, and LXR ligand-mediated inhibition on ANP mRNA expression by T0901317 is receptor dependent.

Protective effect of HDL on endothelial NO production: the role of DDAH/ADMA pathway.

Accumulating studies have demonstrated that the dimethylarginine dimethylaminohydrolase/asymmetric dimethylarginine (DDAH/ADMA) system is a novel pathway for modulating nitric oxide (NO) production. The aim of this study was to investigate whether the protective effect of high density lipoprotein (HDL) on endothelial NO production was related to its effect on DDAH/ADMA pathway. Human umbilical vein endothelial cells (HUVECs) were prior exposed to HDL (10, 50, or 100 µg/ml) for 1 h, and then incubated with oxidized low density lipoprotein (ox-LDL) (100 µg/ml) for 24 h. The cultured medium was collected for measuring the concentration of NO and ADMA. The cells were collected for measuring the mRNA and protein expression of DDAH-II as well as DDAH activity. HUVECs treated with ox-LDL (100 µg/ml) for 24 h significantly decreased the concentration of NO, the mRNA and protein expression of DDAH-II as well as DDAH activity and increased the level of ADMA. Pretreatment with HDL (10, 50, or 100 µg/ml) could counteract these changes induced by ox-LDL (100 µg/ml). HDL significantly increased the attenuated endothelial cell NO production induced by ox-LDL, which was attributed to its effect on DDAH/ADMA pathway.

New insights into the mechanism of low high-density lipoprotein cholesterol in obesity.

Obesity, a significant risk factor for various chronic diseases, is universally related to dyslipidemia mainly represented by decreasing high-density lipoprotein cholesterol (HDL-C), which plays an indispensible role in development of cardiovascular disease (CVD). However, the mechanisms underlying obesity and low HDL-C have not been fully elucidated. Previous studies have focused on the alteration of HDL catabolism in circulation following elevated triglyceride (TG). But recent findings suggested that liver and fat tissue played pivotal role in obesity related low HDL-C. Some new molecular pathways like microRNA have also been proposed in the regulation of HDL metabolism in obesity. This article will review recent advances in understanding of the potential mechanism of low HDL-C in obesity.

[Effects of soluble epoxide hydrolase inhibitors on lipid metabolism and secretive functions of adipocytes].

OBJECTIVE: To observe the effects of soluble epoxide hydrolase inhibitors-tAUCB on the uptake and degradation of ox-LDL in adipocytes. METHODS: 3T3-L1 preadipocytes were induced into differentiation and maturation. After a 24-hour starvation, the cells were stimulated with 100 ng/ml LPS and then tAUCB at various concentrations (0 - 100 µmol/L)were added for 24 h, or preincubated with the PPARγ (peroxisome proliferators activated receptor gamma) antagonist GW9662 (5 µmol/L). And the 0 µmol/L tAUCB-treated group was taken as the blank control group. Then the uptake and degradation of ox-LDL in cells were measured by radioligand assay. The mRNA expressions of PPARγ and CD36 were detected by real-time PCR (polymerase chain reaction). And the intracellular levels of protein expression of PPARγ and CD36 were detected by Western blot. While ADP and TNF-α in supernatant were detected by ELISA. RESULTS: tAUCB could dose-dependently increase the uptake and degradation of ox-LDL in adipocytes. When stimulated with 10, 50, 100 µmol/L tAUCB, the uptake levels of ox-LDL were (35.6 ± 1.1)ng/mg, (39.8 ± 1.6) ng/mg, (42.6 ± 1.4) ng/mg cell protein and the degradation levels of ox-LDL (2879 ± 54) ng/mg, (3082 ± 56) ng/mg, (3226 ± 68) ng/mg cell protein. And they were significantly higher than those of the control group (28.9 ± 1.2) ng/mg, (2791 ± 54) ng/mg respectively (all P < 0.05). However, after preincubation of GW9662, the uptake of ox-LDL were decreased to (30.6 ± 1.3) ng/mg, (31.1 ± 1.7) ng/mg, (32.1 ± 1.8) ng/mg cell protein whereas the degradation of ox-LDL decreased to (2788 ± 53) ng/mg, (2824 ± 70) ng/mg, (2874 ± 70) ng/mg cell protein. And the difference was statistically significant when it was compared with the corresponding tAUCB-treated group. With the rising concentration of tAUCB, tAUCB could dose-dependently increase the mRNA and protein expression of CD36 and PPARγ. tAUCB could dose-dependently decrease the levels of TNF-α and increase the levels of ADP in adipocytes. GW9662 could significantly inhibit those effects of tAUCB and reduce the uptake and degradation of ox-LDL and the expression of PPARγ and CD36 in adipocytes. CONCLUSION: tAUCB can up-regulate the PPARγ expression in adipocytes and promote the uptake and degradation of ox-LDL in adipocytes via PPARγ-CD36 pathway. Meanwhile, the levels of ADP and TNF-α may be mediated through the activation of PPARγ.

HDL and immunomodulation: an emerging role of HDL against atherosclerosis.

Changes in plasma lipoprotein profiles, particularly low levels of high-density lipoprotein (HDL) cholesterol, are associated with several inflammatory and immune diseases, including atherosclerosis and rheumatoid arthritis, implying the potential link between HDL and immunity. Accumulating evidence suggests that HDL possesses anti-inflammatory effects and has an important function in host defense as part of the innate immune system. In addition, HDL inhibits the ability of antigen-presenting cells (APCs) to stimulate T cells. It is subsequently discovered that HDL or HDL-associated platelet-activating factor-acetylhydrolase can restore the emigratory process of monocyte-derived dendritic cells and thus result in resolution of inflammatory reactions in atherosclerotic plaques. Lipid rafts in plasma membrane are the key structure responsible for the immunomodulation effects of HDL, the remarkable ability of HDL to regulate innate and adaptive immune responses extends our understanding of its atheroprotective role, and provides new therapeutic approaches to atherosclerosis and other inflammatory conditions.

Increased soluble OX40L is associated with carotid intima-media thickness.

BACKGROUND: Recent studies indicated that soluble OX40 ligand (OX40L) levels were increased in acute coronary syndrome. But the association between sOX40L and carotid intima-media thickness (IMT) has not been evaluated. METHODS: We measured plasma soluble OX40L (sOX40L) and Interleukin-10 (IL-10) levels in 35 patients with stable angina pectoris, 30 patients with risk factors of coronary artery disease, and 20 age and sex-matched controls. Carotid (IMT) was measured by B-mode ultrasound. RESULTS: Plasma sOX40L levels were positively correlated with Carotid IMT (r = 0.376, P = 0.001) and inversely correlated with IL-10 (P = -0.394, P = 0.000). Multivariate linear regression analysis revealed that sOX40L (p = 0.019) was an independent predictor for Carotid IMT progression after adjusting for the classical cardiovascular risk factors. CONCLUSIONS: sOX40L is independently related to Carotid IMT, suggesting the possible relationship of OX40L to atherosclerosis. The positive relation of sOX40L to C-reactive protein (CRP) and the negative relation to IL-10 indicated the possible proinflammatory effects of OX40L on the pathogenesis of atherosclerois.

[Association between adipocyte fatty acid binding proteins/adiponectin and coronary artery stenosis].

OBJECTIVE: To observe the relationship between serum and monocyte-derived-macrophages secreted adipocyte fatty acid binding protein (A-FABP), adiponectin (or A-FABP/adiponectin ratio) and coronary artery disease. METHODS: Three hundred and forty subjects underwent coronary angiography (CAG) were classified into CAD group (n = 211) and non-CAD group (n = 129) according to the CAG results. The severity of coronary artery stenosis was assessed by the numbers of involved coronary artery branches and the sum of the Gensini scores. Fasting venous blood was collected from all subjects and peripheral monocytes were isolated from 20 subjects (10 selected from each group with age-, gender-, and BMI-matched). Peripheral blood monocytes were obtained and stimulated into macrophages with PMA, cell culture supernatant was collected. The concentration of serum/supernatant A-FABP and adiponectin levels were assayed by enzyme-linked immunosorbent assays. RESULTS: (1) A-FABP levels tended to be higher in CAD patients compared to non-CAD subjects [18.3(13.2, 22.8) µg/L vs. 16.4(13.5, 20.4) µg/L, P = 0.088]. The concentration of adiponectin in CAD group was significantly lower than those in non-CAD group [13.9 (9.8, 17.1) mg/L vs. 19.7 (14.5, 27.6) mg/L, P < 0.05]. (2) The A-FABP levels increased and the adiponectin levels decreased as the number of stenotic vessels increased. Gensini scores were positively correlated with serum A-FABP (r = 0.120, P = 0.043) and inversely correlated with adiponectin (r = -0.405, P = 0.007). (3) The difference in A-FABP/adiponectin ratio was more prominent between subjects with CAD and subjects without CAD [(1.51 ± 0.79) µg/mg vs. (0.89 ± 0.30) µg/mg, P < 0.01] and there was a stronger positive correlation of Gensini score to A-FABP/adiponectin ratio(r = 0.531, P = 0.000). (4) Monocyte-derived-macrophages from patients with CAD had higher A-FABP/adiponectin ratio than that in patients without CAD [(0.51 ± 0.19) µg/mg vs. (0.36 ± 0.11) µg/mg, P < 0.05]. CONCLUSIONS: Increased levels of serum A-FABP and reduced levels of adiponectin in CAD patients serves as a novel biomarker for the severity of the coronary stenosis. A-FABP/adiponectin ratio is superior to A-FABP or adiponectin alone on predicting CAD risks.