J Atheroscler Thromb
· 2026 Jan · PMID 40967771
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Inflammation plays a crucial role in the initiation, progression, and destabilization of atherosclerotic plaques and it contributes to recurrent cardiovascular events in patients with coronary artery disease (CAD). High-...Inflammation plays a crucial role in the initiation, progression, and destabilization of atherosclerotic plaques and it contributes to recurrent cardiovascular events in patients with coronary artery disease (CAD). High-sensitivity C-reactive protein (hsCRP) is a well-established biomarker of systemic inflammation and it is a predictor of adverse outcomes, independent of low-density lipoprotein cholesterol (LDL-C) levels. Elevated hsCRP levels are consistently associated with higher event rates in both chronic and acute coronary syndromes, thus reflecting the residual inflammatory risk not addressed by lipid-lowering therapy or revascularization. Imaging studies have revealed that higher hsCRP levels correlate with a greater plaque burden and vulnerability. Recent trials have shown that anti-inflammatory therapies, including low-dose colchicine and interleukin-6 inhibition, can reduce this residual risk, while agents such as glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, and bempedoic acid offer additional anti-inflammatory effects. The integration of anti-inflammatory strategies with intensive lipid management may thus provide additional cardiovascular benefits.
Hirano T, Takeda Y, Sakuma I
… +4 more, Hiramitsu S, Okada M, Ueda S, Sakurai M
J Atheroscler Thromb
· 2026 Feb · PMID 40967770
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AIM: Overproduction of large very low-density lipoprotein1 (VLDL1) is a central abnormality in metabolic dyslipidemia. Excess-triglycerides (Ex-TG), based on the Friedewald equation, is considered to be a marker for TG-r...AIM: Overproduction of large very low-density lipoprotein1 (VLDL1) is a central abnormality in metabolic dyslipidemia. Excess-triglycerides (Ex-TG), based on the Friedewald equation, is considered to be a marker for TG-rich VLDL, but it remains uncertain whether Ex-TG reflects large VLDL particles. METHODS: We conducted a retrospective sub-analysis of the PROUD48 study, which compared the effects of pemafibrate and omega-3 fatty acids (FAs) on apolipoprotein B48, with data available on VLDL subfractions. Hyperlipidemic patients on statins were treated with pemafibrate (n = 56) or omega-3FAs (n = 56) for 16 weeks. VLDL subfractions: large (L), middle (M), and small (S) were separated using high-performance liquid chromatography. Ex-TG was calculated as plasma TG minus 5 x calculated VLDL-cholesterol (C).Calculated VLDL=total-C minus directly measured LDL-C minus HDL-C. RESULTS: Pemafibrate and omega-3FAs reduced plasma TG levels by 42% and 27%, respectively; however, a marked reduction in Ex-TG was observed only with omega-3 FAs. Ex-TG was positively correlated with L-VLDL-TG, %L-VLDL-TG, (L-M+S)-VLDL-TG, and L-VLDL-TG/C, while it showed no positive correlation with smaller VLDLs and apoB48. TG exhibited stronger correlations with L-VLDL-related parameters than Ex-TG, but was also positively associated with smaller VLDLs and apoB48. These correlation patterns remained consistent even when examining the relationship between changes in Ex-TG, TG, or apoB48 and corresponding changes in VLDL subfractions using lipid-lowering agents. CONCLUSIONS: The behavior of Ex-TG appears consistent with previous kinetic studies showing that omega-3FAs primarily suppress VLDL1 production, whereas fibrates promote TG removal, suggesting that Ex-TG serves as a surrogate marker for VLDL1 overproduction.
J Atheroscler Thromb
· 2026 Jan · PMID 40930795
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AIMS: The phase angle (PhA) derived from a bioelectrical impedance analysis (BIA) is a risk factor for cardiovascular disease (CVD). The present study explored the relationship between PhA and the progression of subclini...AIMS: The phase angle (PhA) derived from a bioelectrical impedance analysis (BIA) is a risk factor for cardiovascular disease (CVD). The present study explored the relationship between PhA and the progression of subclinical atherosclerosis in asymptomatic adults. METHODS: Two cross-sectional studies were performed on 15579 participants who underwent carotid ultrasound testing and a BIA as well as 8228 participants who underwent brachial ankle pulse wave velocity (baPWV) testing and a BIA. We also conducted a longitudinal study in participants without CVD and carotid atherosclerosis (CAS) at baseline who underwent carotid ultrasound ≥ 2 times (n = 2680) or baPWV testing [≥ 2 times] (n = 1775). CAS and the brachial ankle pulse wave velocity (baPWV) were selected as the subclinical atherosclerosis markers. RESULTS: In the cross-sectional studies, participants with CAS (5.43±0.60° vs. 5.73±0.61°, P＜0.001) or elevated baPWV (5.38±0.62° vs. 5.74±0.59°, P＜0.001) had lower PhA values than controls. Furthermore, the PhA value was independently and inversely correlated with CAS (adjusted odds ratio [OR] = 0.41, 95% confidence interval [CI] 0.37-0.46, P＜0.001) and elevated baPWV (adjusted OR = 0.45, 95% CI 0.39-0.52, P＜0.001). Restricted cubic spline curve analyses indicated dose-response associations of PhA values with subclinical atherosclerosis. In the longitudinal study, high PhA values at baseline decreased the risk of incident CAS (adjusted hazard ratio = 0.44, 95% CI 0.36-0.54, P＜0.001). Multivariate linear regression analyses showed that the PhA was negatively associated with absolute or relative annual changes in baPWV. CONCLUSION: The PhA value is significantly associated with the progression of subclinical atherosclerosis, indicating that PhA may serve as a noninvasive marker for monitoring subclinical atherosclerosis in a primary prevention setting.
Tong D, Kong L, Song B
… +9 more, Wu W, Li G, Xie F, Wang H, Zhang C, Liu Y, Shao Y, Xia W, Li J
J Atheroscler Thromb
· 2026 Feb · PMID 40930794
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AIMS: In-stent restenosis (ISR) is a significant limitation of coronary stent implantation, but the exact mechanism of ISR remains unclear. Patients after percutaneous coronary intervention (PCI) are in a hypercoagulable...AIMS: In-stent restenosis (ISR) is a significant limitation of coronary stent implantation, but the exact mechanism of ISR remains unclear. Patients after percutaneous coronary intervention (PCI) are in a hypercoagulable state; however, there is less information on its association with chronic coronary artery disease (CAD) in patients with ISR after PCI. We aimed to clarify whether or not CAD patients with ISR after PCI are in a hypercoagulable state and whether or not PS exposure on extracellular vesicles (EVs), blood cells (BCs), and endothelial cells (ECs) is involved in the hypercoagulable state. METHODS: Phosphatidylserine (PS) exposure to EVs, BCs, and ECs was analyzed using flow cytometry. Procoagulant activity (PCA) was analyzed by clotting time (CT), purified clotting complex assays, and fibrin production assays. RESULTS: Compared with pre-PCI or controls, levels of exposed PS on EVs, BCs, and ECs were significantly increased from 1 day, peaked at 3 months, and gradually decreased within 1 year in CAD patients after PCI, especially in CAD patients with ISR after PCI. Furthermore, their increased levels significantly decrease CT and enhance intrinsic/extrinsic FXa, thrombin, and fibrin generation. PCA was weakened by approximately 80% when lactadherin was used. CONCLUSIONS: Our results revealed that CAD patients after PCI, especially those patients with ISR after PCI, are associated with a hypercoagulable state in which PS exposure on EVs, BCs, and ECs plays a more important role than tissue factors. Therefore, blocking PS exposure to EVs, BCs, and ECs may provide a new target for preventing ISR in these patients.
Matsuo M, Ogura M, Kuroda M
… +6 more, Arisato T, Kishida M, Harada-Shiba M, Wada J, Yokote K, Yoshihara F
J Atheroscler Thromb
· 2026 Feb · PMID 40930774
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A 79-year-old Chinese man was referred for nephrotic syndrome (proteinuria 4.4 g/day). In blood tests, serum high-density lipoprotein (HDL) cholesterol was undetectable, and the esterified cholesterol to total cholestero...A 79-year-old Chinese man was referred for nephrotic syndrome (proteinuria 4.4 g/day). In blood tests, serum high-density lipoprotein (HDL) cholesterol was undetectable, and the esterified cholesterol to total cholesterol ratio was very low. Lecithin: cholesterol acyltransferase (LCAT) activity was also undetectable. Since he had neither corneal opacity nor pathological mutations in the LCAT gene and anti-LCAT antibodies were detected in serum, a diagnosis of acquired LCAT deficiency was made. Renal biopsy revealed glomerulopathy associated with LCAT deficiency and membranous nephropathy (MN). Since the patient's proteinuria did not improve despite prescribing an angiotensin II receptor blocker (ARB), we suggested the prescription of prednisolone, but he returned to China due to the expiration of his residence visa for Japan. One year after the initial visit, his proteinuria had improved to 0.9 g/day without immunosuppressive therapy. However, his HDL cholesterol level was still low at around 3 mg/dL, indicating a discrepancy between remission of nephrotic syndrome and lack of improvement in lipid levels.Of the 11 patients with acquired LCAT deficiency reported to date, 4 with undetectable LCAT activity and MN on renal biopsy required immunosuppressive therapy to alleviate proteinuria. The present patient was prescribed only an ARB according to his preference, which happened to be consistent with the MN treatment guideline that states, "Wait 6 months for spontaneous remission while using maximal antiproteinuric therapy." The clinical course of acquired LCAT deficiency varies, and further case reports are needed to determine the necessity of immunosuppressive therapy.
Arai S, Hoshino T, Mizuno T
… +7 more, Ishizuka K, Hosoya M, Takahashi S, Wako S, Toi S, Kitagawa K, Todo K
J Atheroscler Thromb
· 2026 Feb · PMID 40903306
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AIMS: Interleukin-6 (IL-6) is a cytokine involved in the development of atherosclerosis and ischemic stroke. Herein, we investigated the association between serum IL-6 levels at stroke onset and long-term outcomes in pat...AIMS: Interleukin-6 (IL-6) is a cytokine involved in the development of atherosclerosis and ischemic stroke. Herein, we investigated the association between serum IL-6 levels at stroke onset and long-term outcomes in patients with ischemic stroke. METHODS: This prospective observational study enrolled 655 consecutive patients (mean age, 70 years; male, 62.1%) with ischemic stroke within one week of onset followed-up for one year. Patients were divided into 3 groups according to baseline serum IL-6 tertiles: tertile 1, ＜2.6 pg/mL (n = 216); tertile 2, 2.6-6.1 pg/mL (n = 217); and tertile 3, ＞= 6.2 pg/mL (n = 222). We evaluated the association of serum IL-6 levels with a composite of major adverse cardiovascular events (MACE; nonfatal stroke, nonfatal acute coronary syndrome, major peripheral artery disease, and vascular death) and the poor functional outcome defined as modified Rankin Scale score of ≥ 3 at one year. RESULTS: Higher serum IL-6 levels were associated with increased prevalence of chronic kidney disease, atrial fibrillation, chronic heart disease, active cancer, and post-stroke pneumonia. The three groups showed significant differences in the one-year MACE risk (annual rate, 11.2%, 10.8%, and 19.1% in the tertiles 1, tertile 2, and tertile 3 groups, respectively). Higher serum IL-6 levels were significantly associated with poor functional outcomes at one year after stroke (14.4%, 29.5%, and 56.8% in the tertile 1, tertile 2, and tertile 3 groups, respectively; P＜0.001), even when adjusting for baseline covariates and MACE during follow-up. CONCLUSIONS: Higher serum IL-6 level at ischemic stroke onset was an independent predictor of poor functional prognosis at one year.
Suzuki H, Ogura M, Kakita H
… +4 more, Endo T, Tsukamoto T, Harada-Shiba M, Muso E
J Atheroscler Thromb
· 2026 Feb · PMID 40903305
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AIM: This study addressed the alteration and related factors of cholesterol efflux capacity (CEC) and anti-oxidative activity in patients with chronic kidney disease (CKD). METHODS: This retrospective cross-sectional obs...AIM: This study addressed the alteration and related factors of cholesterol efflux capacity (CEC) and anti-oxidative activity in patients with chronic kidney disease (CKD). METHODS: This retrospective cross-sectional observational study included 333 patients (median age: 50 [20, 81] years old, male: 46.5%) who underwent a kidney biopsy at Kitano Hospital. CEC and oxygen radical adsorption capacity (ORAC) were measured using serum obtained at the time of the kidney biopsy. Changes in CEC and ORAC in relation to the clinical and kidney injury parameters were evaluated. RESULTS: Mean CEC and ORAC were 0.83±0.15 and 0.86±0.14, respectively. High-density lipoprotein-cholesterol (HDL-C) levels were significantly associated with CEC (r = 0.673, p＜0.001) and ORAC (r = 0.164, p = 0.003). CEC showed a weak association with ORAC (r = 0.333, p＜0.001). Both HDL-C and CEC were negatively associated with the body mass index (r = -0.407, p＜0.001 and r = -0.248, p＜0.001, respectively) and were significantly higher in women than in men (p＜0.001). The ORAC was positively associated with the serum albumin level (r = 0.330, p＜0.001) and negatively associated with the urinary protein creatinine ratio (UPCR) (r = -0.236, p＜0.001). A multiple regression analysis showed that CEC was associated with the estimated glomerular filtration rate (eGFR), serum albumin, and ORAC. There was no significant correlation between global sclerosis and either CEC or ORAC. CONCLUSIONS: The HDL-C level did not represent HDL functionalities in CKD patients. The decreased eGFR and reduced serum albumin levels induced by an increased UPCR might therefore be associated with impaired HDL functionalities.
J Atheroscler Thromb
· 2025 Nov · PMID 40903276
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High-density lipoprotein (HDL) levels have long been inversely associated with cardiovascular disease (CVD) and are traditionally evaluated by serum HDL-cholesterol (HDL-C) levels. However, recent studies have raised dou...High-density lipoprotein (HDL) levels have long been inversely associated with cardiovascular disease (CVD) and are traditionally evaluated by serum HDL-cholesterol (HDL-C) levels. However, recent studies have raised doubts regarding the causal role of HDL quantity (HDL-C), drawing attention to HDL functionality. Reverse cholesterol transport (RCT) is a major anti-atherosclerotic mechanism involving ATP-binding cassette A1 (ABCA1), ATP-binding cassette G1 (ABCG1), scavenger receptor class B type I (SRB1), and regulatory factors, such as liver X receptor (LXR) and peroxisome proliferator-activated receptor gamma (PPARγ). Notably, HDL-C levels do not necessarily reflect RCT efficiency, and novel regulatory factors, such as microRNAs, endothelial lipase, and ANGPTL3, have been implicated. HDL also exhibits vasoprotective functions by enhancing nitric oxide (NO) production and modulating sphingosine-1-phosphate (S1P) signaling. Furthermore, it exerts anti-inflammatory effects by suppressing adhesion molecules, proinflammatory cytokines, and innate immune activation while modulating adaptive immune responses and attenuating tissue fibrosis. In addition, HDL influences megakaryopoiesis and platelet activation, thereby contributing to its antithrombotic properties. Despite these broad functional spectra, clinical assessments remain largely limited to cholesterol efflux capacity, and other key functional aspects have not been adequately explored. A more comprehensive understanding of HDL's pleiotropic roles, spanning lipid metabolism, vascular biology, inflammation, and hemostasis, is necessary from both the basic and clinical perspectives. Recent studies have further suggested potential roles of HDL in the central nervous system, expanding its relevance beyond cardiovascular prevention and toward broader therapeutic applications.
Nakahashi T, Tada H, Sakata K
… +1 more, Takamura M
J Atheroscler Thromb
· 2025 Dec · PMID 40887304
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Hyperuricemia, the biochemical precursor to gout, is usually defined as the theoretical limit of solubility of serum uric acid (UA) of ＞7.0 mg/dL. Hyperuricemia is closely associated with hypertension, diabetes mellitus...Hyperuricemia, the biochemical precursor to gout, is usually defined as the theoretical limit of solubility of serum uric acid (UA) of ＞7.0 mg/dL. Hyperuricemia is closely associated with hypertension, diabetes mellitus, and dyslipidemia, which are well known to be related to risk factors for coronary artery disease (CAD). Furthermore, hyperuricemia has been associated with increased mortality in both the general population and individuals with cardiovascular diseases. Elevated UA in patients with CAD is accompanied by surrogate markers of atherosclerosis, including C-reactive protein, platelet activation, and endothelial dysfunction, which can contribute to possible pathogenic links between hyperuricemia and subsequent adverse cardiovascular events. Similarly, patients with gout have higher rates of cardiovascular diseases than those without it, independent of traditional cardiovascular risk factors. Gout is a disease with variable levels of inflammation, driven by deposition of monosodium urate (MSU) crystals. Recent imaging technology has revealed that deposition of MSU crystals can occur in the coronary arteries as well as the joints. However, current evidence does not support the efficacy of urate-lowering therapy on reducing cardiovascular events in patients with hyperuricemia; therefore, identifying individuals who may benefit from a sustained decrease in UA is crucial. We herein review the current understanding and future perspectives for management of hyperuricemia as a residual risk in patients with CAD.
Hu H, Nakagawa T, Honda T
… +12 more, Yamamoto S, Okazaki H, Ide H, Dohi S, Miyamoto T, Yamamoto M, Gommori N, Kochi T, Ogasawara T, Konishi M, Kabe I, Mizoue T
J Atheroscler Thromb
· 2026 Feb · PMID 40887303
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AIMS: This study examined whether or not the coexistence of smoking and metabolic syndrome synergistically increases the risk of cardiovascular disease (CVD) beyond their individual effects. METHODS: This prospective coh...AIMS: This study examined whether or not the coexistence of smoking and metabolic syndrome synergistically increases the risk of cardiovascular disease (CVD) beyond their individual effects. METHODS: This prospective cohort study included 68,743 workers from the Japan Epidemiology Collaboration on Occupational Health Study. The participants were categorized into four groups based on their smoking status and metabolic syndrome. Biological interactions were evaluated using relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S). RESULTS: During a mean follow-up of 7.2 (range: 0.1-10.9) years, 346 participants developed CVD. Current smokers with metabolic syndrome had the highest CVD risk (hazard ratio: 6.45, 95% confidence interval [CI]: 4.73-8.80). Approximately 35% of CVD cases among individuals exposed to both factors were attributed to their biological interactions (RERI: 2.27, 95% CI: 0.56-3.98; AP: 0.35, 95% CI: 0.15-0.55; S: 1.71, 95% CI: 1.16-2.52). An analysis of CVD subtypes revealed a significant biological interaction for myocardial infarction (RERI: 5.14, 95% CI: 0.65-9.62; AP: 0.52, 95% CI: 0.26-0.78; S: 2.38, 95% CI: 1.22-4.62) but not for stroke (RERI: 1.34, 95% CI: -0.46-3.13; AP: 0.25, 95% CI: -0.03-0.53; S: 1.44, 95% CI: 0.89-2.34). CONCLUSION: Smoking and metabolic syndrome interact synergistically to elevate CVD risk, particularly for myocardial infarction. Targeting both factors is essential for CVD prevention.
Liu J, Chen X, Liang Y
… +5 more, Liu D, Cheng X, Qu Y, Zhou H, Guo ZN
J Atheroscler Thromb
· 2026 Feb · PMID 40866223
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AIM: Intracranial artery calcification (IAC) in patients with acute ischemic stroke may cause cerebral hemodynamic injury and aggravate ischemia-reperfusion injury. However, its relationship with brain damage and clinica...AIM: Intracranial artery calcification (IAC) in patients with acute ischemic stroke may cause cerebral hemodynamic injury and aggravate ischemia-reperfusion injury. However, its relationship with brain damage and clinical outcomes has not yet been fully explored. METHODS: Patients with acute anterior circulation ischemic stroke who underwent intravenous thrombolysis (IVT) were enrolled. Intracranial artery calcification (IAC) was assessed using the IAC volume and number of calcified vessels (NCV) on pre-IVT computed tomography. Outcomes included the degree of brain injury at 24 h post-IVT, measured by serum glial fibrillary acidic protein (GFAP) levels, final infarct volumes, intracranial hemorrhaging within 24 h of IVT, and a poor prognosis at 90 days (modified Rankin Scale ＞2). A multivariate regression analysis was conducted to evaluate the associations between IAC parameters and clinical outcomes. RESULTS: A total of 348 patients were enrolled in the study, of whom 273 (78.4%) had IAC. Patients were divided into four quartile groups (Q1, Q2, Q3, and Q4) based on the total IAC volume. The fourth quartile (Q4), which included patients with the highest IAC volume, was independently associated with elevated GFAP levels (odds ratio [OR] = 2.449, 95% confidence interval [CI], 1.057-5.673; P = 0.037). The second quartile (Q2) was independently associated with final infarct volume (β:0.483, 95% CI:0.014-0.952, P = 0.044). In addition, NCV was independently correlated with increased GFAP levels (OR = 1.265, 95% CI:1.010-1.584, P = 0.040) and a poor prognosis (OR = 1.270, 95% CI: 1.008-1.600, P = 0.043). CONCLUSION: IAC was independently associated with the degree of brain injury, final infarct volume, and prognosis in patients after IVT.
Komatsu T, Abe S, Kuroda M
… +11 more, Endo Y, Sasaki K, Nishida T, Teramoto M, Arakawa J, Kuwata K, Imakiire T, Maezawa Y, Yokote K, Uehara Y, Ikewaki K
J Atheroscler Thromb
· 2025 Dec · PMID 40850751
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Familial lecithin-cholesterol acyltransferase (LCAT) deficiency with a primary LCAT gene mutation results in various conditions, including corneal opacity, anemia, kidney disease, and low high-density lipoprotein (HDL) l...Familial lecithin-cholesterol acyltransferase (LCAT) deficiency with a primary LCAT gene mutation results in various conditions, including corneal opacity, anemia, kidney disease, and low high-density lipoprotein (HDL) levels. In recent years, secondary LCAT deficiency with nearly identical symptoms has been identified as a rare case of immune-mediated acquired LCAT deficiency caused by LCAT autoantibodies. In limited cases, prednisolone treatment is required for severe conditions and has been shown to favorably modulate LCAT autoantibodies and restore LCAT activity, resulting in improved HDL-cholesterol (HDL-C) levels, renal dysfunction, and other complications. However, there is little detailed information regarding LCAT activity, lipid changes, and renal dysfunction after the initiation of prednisorone treatment. In the present study, in addition to the effects on LCAT activity, lipids, and proteinuria, we for the first time monitored the HDL cholesterol efflux capacity (CEC), an important anti-atherosclerotic HDL function, during the first month of treatment in a patient with this disease. We found that the LCAT activity, HDL-C concentration, and HDL CEC increased from undetectable or low values to normal ranges during this period, as did proteinuria. Specifically, the HDL CEC and LCAT activity recovered faster than the HDL-C levels. Based on these findings, the effects of prednisolone treatment on LCAT and HDL CEC activities prior to HDL-C levels suggest that normal HDL-C levels may not be essential as a treatment target in immune-mediated acquired LCAT deficiency patients who require treatment.
J Atheroscler Thromb
· 2026 Jan · PMID 40850750
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AIMS: MN-001 (tipelukast), a compound with lipid-modulating and anti-inflammatory properties, and its active metabolite MN-002, have been suggested to influence cholesterol metabolism. This study aimed to investigate whe...AIMS: MN-001 (tipelukast), a compound with lipid-modulating and anti-inflammatory properties, and its active metabolite MN-002, have been suggested to influence cholesterol metabolism. This study aimed to investigate whether MN-001 and MN-002 enhance cholesterol efflux via ABCA1 and ABCG1, thereby reducing foam cell formation. We also evaluated cholesterol efflux capacity in patients with diabetes before and after MN-001 administration. METHODS: Cholesterol efflux was assessed in THP-1 macrophages treated with MN-001 and MN-002 in the presence of ApoA-I or HDL. ABCA1 and ABCG1 expression were evaluated using western blot and qPCR analyses. A 12-week observational study in patients with diabetes evaluated the cholesterol efflux capacity using ApoB-depleted serum and radiolabeled J774.1 macrophages. Molecular docking simulations were conducted to explore MN-002 binding affinities, aiming to identify potential target proteins and elucidate the molecular mechanisms underlying their effects on cholesterol metabolism. RESULTS: MN-002 enhanced ABCA1-mediated cholesterol efflux and upregulated ABCA1 expression independently of PKA. It also increased ABCG1 expression; however, neither MN-001 nor MN-002 influenced HDL-mediated efflux. MN-001 showed no significant improvement in cholesterol efflux capacity (p = 0.6507) in patients with diabetes. Molecular docking simulations indicated that MN-002 may bind to PPAR-alpha, suggesting a potential mechanism for its effects. CONCLUSION: MN-002 offers a novel therapeutic approach for atherosclerosis by upregulating ABCA1 and ABCG1 expression and enhancing ApoA-I-mediated cholesterol efflux. Further studies are required to clarify the underlying mechanisms and assess their clinical potential in atherosclerosis and metabolic disorders.
Ni P, Li J, Duan Y
… +7 more, Hu P, Deng Q, Hao Y, Yang Z, Han L, Qi Y, Liu J
J Atheroscler Thromb
· 2026 Jan · PMID 40835444
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AIM: Mounting evidence suggests apolipoprotein E-containing high-density lipoprotein cholesterol (APOE-HDLC) as an indicator of the anti-atherogenic function of HDLC, but data are lacking on whether or not APOE-HDLC is i...AIM: Mounting evidence suggests apolipoprotein E-containing high-density lipoprotein cholesterol (APOE-HDLC) as an indicator of the anti-atherogenic function of HDLC, but data are lacking on whether or not APOE-HDLC is involved in the development of atherosclerosis in humans. This study was performed to explore whether or not APOE-HDLC is associated with atherosclerotic plaque progression in humans. METHODS: Among 823 participants 45 to 74 years old who were free of cardiovascular disease, we assessed nuclear magnetic resonance spectroscopy-measured HDL particle concentrations, APOE-HDLC levels and HDLC levels at baseline, and performed carotid ultrasound measurements in surveys conducted in 2002 and again in 2007 after a 5-year interval. The ratio of APOE-HDLC to total HDLC (APOE-HDLC/HDLC ratio) was calculated to assess the relative proportion of APOE-HDLC in total HDLC, given the strong correlation between them. RESULTS: The baseline APOE-HDLC/HDLC ratio was significantly associated with the risk of 5-year plaque progression (relative risk [RR] = 0.71; 95% confidence interval [CI] = 0.53-0.95), which is independent of the ratio of HDLC to the HDL particle number (HDLC/P ratio). In particular, participants with an HDLC/P ratio ≥ 44.8 (denoted very high level of cholesterol content per HDLP, a marker of dysfunctional HDL) had a 36% reduced 5-year plaque progression risk (RR = 0.64; 95% CI = 0.43-0.97) if combined with the highest APOE-HDLC/HDLC ratio, as compared with the lowest APOE-HDLC/HDLC ratio. CONCLUSIONS: These results highlight the potential utility of APOE-containing HDL as a candidate emerging biomarker for the anti-atherosclerotic function of HDL particles.
J Atheroscler Thromb
· 2025 Oct · PMID 40803871
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Pediatric lifestyle disease screening in Japan plays a crucial role in the early detection of obesity, dyslipidemia, hypertension, and type 2 diabetes. However, it is not mandated by national law, instead being conducted...Pediatric lifestyle disease screening in Japan plays a crucial role in the early detection of obesity, dyslipidemia, hypertension, and type 2 diabetes. However, it is not mandated by national law, instead being conducted independently by local governments, which results in significant regional disparities. While many programs focus only on obese children, this approach risks missing high-risk individuals with normal weight, such as those with familial hypercholesterolemia (FH) or non-obese type 2 diabetes. Regional initiatives in cities such as Fukuoka, Niigata, Kumamoto, and Kitakyushu have demonstrated various effective models, including the use of growth and obesity curves, expanded screening parameters, and school-healthcare collaborations. National surveys show that fewer than 30% of municipalities conduct such screenings, often with limited standardization. Kagawa Prefecture presents a notable example of integrating FH screening with lifestyle checkups to achieve high participation and follow-up rates. To expand and improve its effectiveness, universal screening based on standardized criteria is essential. Efforts should also focus on public education, early intervention, and coordinated systems involving school nurses and teachers, pediatricians and family doctors, local medical associations, educational boards, and municipal health authorities. Universal screening, combined with individualized follow-up and strong community collaboration, can help healthcare providers, educators, and local governments in Japan respond more effectively to the growing prevalence of pediatric obesity and metabolic disorders. This approach also promotes equitable access to preventive care for children.
Sakurabu Y, Uchida HA, Okuyama Y
… +13 more, Eto E, Takasugi K, Asakawa T, Katayama K, Okamoto S, Onishi Y, Matsuoka-Uchiyama N, Fujihara C, Tanaka K, Takeuchi H, Umebayashi R, Tanabe K, Wada J
J Atheroscler Thromb
· 2026 Jan · PMID 40803869
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Familial hypercholesterolemia (FH) is an inherited disorder characterized by elevated LDL cholesterol levels and an increased risk of early-onset atherosclerotic cardiovascular disease. In pregnant female with FH, aphere...Familial hypercholesterolemia (FH) is an inherited disorder characterized by elevated LDL cholesterol levels and an increased risk of early-onset atherosclerotic cardiovascular disease. In pregnant female with FH, apheresis is the preferred treatment because standard therapeutic agents such as statins are contraindicated during pregnancy. LDL adsorption therapy is commonly used; however, after 27 weeks of gestation, it is often switched to dual filtration plasma exchange (DFPP) due to the significant drop in blood pressure caused by bradykinin production. However, DFPP has limited ability to adapt to the increase in circulating plasma volume associated with pregnancy. Here we discuss the case of a 32-year-old female with homozygous FH who underwent different apheresis strategies during her pregnancies. In her first pregnancy, she continued LDL adsorption therapy using DFPP but ultimately delivered a small-for-gestational-age infant via cesarean section. For her second pregnancy, double-filtration plasmapheresis thermo mode, DF-thermo, was introduced to mitigate the limitations of DFPP and LDL adsorption therapies, such as hypotension during apheresis and albumin loss. By minimizing these complications, DF-thermo allowed for a successful delivery without compromising fetal growth.