Apolipoprotein O modulates cholesterol metabolism via NRF2/CYB5R3 independent of LDL receptor.

Apolipoprotein O (APOO) plays a critical intracellular role in regulating lipid metabolism. Here, we investigated the roles of APOO in metabolism and atherogenesis in mice. Hepatic APOO expression was increased in response to hyperlipidemia but was inhibited after simvastatin treatment. Using a novel APOO global knockout (Apoo-/-) model, it was found that APOO depletion aggravated diet-induced obesity and elevated plasma cholesterol levels. Upon crossing with low-density lipoprotein receptor (LDLR) and apolipoprotein E (APOE) knockout hyperlipidemic mouse models, Apoo-/- Apoe-/- and Apoo-/- Ldlr-/- mice exhibited elevated plasma cholesterol levels, with more severe atherosclerotic lesions than littermate controls. This indicated the effects of APOO on cholesterol metabolism independent of LDLR and APOE. Moreover, APOO deficiency reduced cholesterol excretion through bile and feces while decreasing phospholipid unsaturation by inhibiting NRF2 and CYB5R3. Restoration of CYB5R3 expression in vivo by adeno-associated virus (AAV) injection reversed the reduced degree of phospholipid unsaturation while decreasing blood cholesterol levels. This represents the first in vivo experimental validation of the role of APOO in plasma cholesterol metabolism independent of LDLR and elucidates a previously unrecognized cholesterol metabolism pathway involving NRF2/CYB5R3. APOO may be a metabolic regulator of total-body cholesterol homeostasis and a target for atherosclerosis management. Apolipoprotein O (APOO) regulates plasma cholesterol levels and atherosclerosis through a pathway involving CYB5R3 that regulates biliary and fecal cholesterol excretion, independently of the LDL receptor. In addition, down-regulation of APOO may lead to impaired mitochondrial function, which in turn aggravates diet-induced obesity and fat accumulation.

Metformin-induced PCSK9 inhibition further decreases LDL-C following statin treatment in patients with coronary artery disease and without diabetes.

In vitro investigations have established metformin's capacity to downregulate PCSK9 expression, suggesting a potential beneficial effect on atherogenic lipoprotein particles when combined with metformin therapy. Our objective was to assess whether metformin could mitigate statin-induced adverse effects on PCSK9, thereby improving lipid profiles in patients with coronary artery disease (CAD) but without diabetes. Employing an open-label, placebo-controlled, randomized trial, we randomized patients with CAD but without diabetes into CLA (Cholesterol-Lowering Agents alone: atorvastatin+/-ezetimibe, n=38) and Met+CLA groups (metformin plus CLA, n=33) at a 1:1 ratio. The primary endpoint was the therapeutic impact of one-month metformin combination treatment on LDL-C and PCSK9 levels. Baseline LDL-C and PCSK9 levels were 76.18 mg·dL-1 and 80.54 ng·mL-1, respectively. After one month, metformin significantly reduced LDL-C (-20.81%, P<0.001), enabling 72% of patients to attain guideline-recommended LDL-C goals. Noteworthy reductions in PCSK9 levels (-15.03%, P<0.001) were observed. Moreover, Met+CLA markedly reduced LDL particle number more than CLA alone (-10.65% vs 1.45%, P=0.009), primarily due to diminished small-dense LDL particle count. Mechanistically, our study demonstrated metformin's inhibition of statin-induced PCSK9 expression in human hepatocellular cells. In summary, a one-month metformin combination regimen reduced LDL-C levels in patients with CAD but without diabetes by inhibiting PCSK9 expression.

Macrophage-specific deletion of MIC26 (APOO) mitigates advanced atherosclerosis by increasing efferocytosis.

BACKGROUND AND AIMS: Recent studies have suggested that MIC26 (apolipoprotein O, APOO), a novel mitochondrial inner membrane protein, is involved in inflammation. Thus, the role of macrophage MIC26 in acute inflammation and chronic inflammatory disease atherosclerosis was investigated. METHODS: Macrophage-specific MIC26 knockout mice (MIC26LysM) were generated by crossing Apooflox/flox and LysMcre+/- mice. An endotoxemia mouse model was generated to explore the effects of macrophage MIC26 deficiency on acute inflammation, while an atherosclerosis mouse model was constructed by crossing MIC26LysM mice with Apoe-/- mice and challenged with a Western diet. Atherosclerotic plaques, primary macrophage function, and mitochondrial structure and function were analyzed. RESULTS: MIC26 knockout did not affect the median survival time and post-injection serum interleukin 1ß concentrations in mice with endotoxemia. Mice with MIC26 deficiency in an Apoe-/- background had smaller atherosclerotic lesions and necrotic core than the control group. In vitro studies found that the loss of MIC26 did not affect macrophage polarization, apoptosis, or lipid handling capacity, but increased efferocytosis (the ability to clear apoptotic cells). An in situ efferocytosis assay of plaques also showed that the ratio of macrophage-associated apoptotic cells to free apoptotic cells was higher in the MIC26-deficient group than in the control group, indicating increased efferocytosis. In addition, an in vivo thymus efferocytosis assay indicated that MIC26 deletion promoted efferocytosis. Mechanistically, the loss of MIC26 resulted in an abnormal mitochondrial inner membrane structure, increased mitochondrial fission, and decreased mitochondrial membrane potential. Loss of MIC26 reduced mitochondria optic atrophy type 1 (OPA1) protein, and OPA1 silencing in macrophages promoted efferocytosis. Overexpression of OPA1 abolished the increase in efferocytosis produced by MIC26 deficiency. CONCLUSIONS: Macrophage MIC26 deletion alleviated advanced atherosclerosis and necrotic core expansion by promoting efferocytosis. This mechanism may be related to the increased mitochondrial fission caused by reduced mitochondrial OPA1.

Loss of APOO (MIC26) aggravates obesity-related whitening of brown adipose tissue via PPARα-mediated functional interplay between mitochondria and peroxisomes.

BACKGROUND: Mitochondrial dysfunction and aberrant structure in adipose tissue occur in obesity and obesity-linked brown adipose tissue (BAT) whitening; however, whether this aberrant architecture contributes to or is the result of obesity is unknown. Apolipoprotein O (APOO) is a constitutive protein of the mitochondrial cristae organizing system complex. This study aimed to characterize the physiological consequences of APOO deficiency in vivo. METHODS: APOO expression was analyzed in different human and murine adipose depots, and mice lacking APOO in adipocytes (ApooACKO) are developed to examine the metabolic consequences of adipocyte-specific APOO ablation in vitro and in vivo. RESULTS: Results showed that APOO expression is reduced in BAT from both diet-induced and leptin-deficient obese mice. APOO-knockout mice showed increased adiposity, BAT dysfunction and whitening, reduced non-shivering thermogenesis, and blunted responses to cold stimuli. APOO deficiency disrupted mitochondrial structure in brown adipocytes and impaired oxidative phosphorylation, thereby inducing a shift from oxidative to glycolytic metabolism, increasing lipogenic enzyme levels and BAT whitening. APOO inactivation inhibited thermogenesis in BAT by reducing mitochondrial long-chain fatty acid oxidation. It also disturbed peroxisomal biogenesis and very long-chain fatty acid oxidation via peroxisome proliferator-activated receptor α. CONCLUSIONS: Altogether, APOO deficiency in adipocytes aggravates BAT whitening and diet-induced obesity; thus, APOO could be a therapeutic target for obesity.

Mechanisms of unusual response to lipid-lowering therapy: PCSK9 inhibition.

The efficacy of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition has broadened lipid-lowering therapy thus providing decreased risk in atherosclerotic cardiovascular disease. Unfortunately, the widespread use of PCSK9 inhibitors (PCSK9i), ie, monoclonal antibodies, has led to the findings of unusual responsiveness, ie, a phenomenon defined as an LDL-C reduction of <30% vs the average LDL-C reduction efficacy of 50-60%. This unusual responsiveness to PCSK9i is attributable to several factors, ie, lack of adherence, impaired absorption, poor distribution or early elimination as well as abnormal effects of PCSK9i in the presence of anti-antibodies or mutations in PCSK9 and LDLR. Unexpectedly increased lipoprotein (Lp)(a) also appear to contribute to the unusual responsiveness scenario. Identification of these responses and mechanisms underlying them are essential for effective management of LDL-C and cardiovascular risk. In this review, we describe plausible reasons underlying this phenomenon supported by findings of clinical trials. We also elaborate on the need for education and regular follow-up to improve adherence. Collectively, the review provides a summary of the past, present, and future of mechanisms and countermeasures revolving around unusual responses to PCSK9i therapy.

Inflamed adipose tissue: A culprit underlying obesity and heart failure with preserved ejection fraction.

The incidence of heart failure with preserved ejection fraction is increasing in patients with obesity, diabetes, hypertension, and in the aging population. However, there is a lack of adequate clinical treatment. Patients with obesity-related heart failure with preserved ejection fraction display unique pathophysiological and phenotypic characteristics, suggesting that obesity could be one of its specific phenotypes. There has been an increasing recognition that overnutrition in obesity causes adipose tissue expansion and local and systemic inflammation, which consequently exacerbates cardiac remodeling and leads to the development of obese heart failure with preserved ejection fraction. Furthermore, overnutrition leads to cellular metabolic reprogramming and activates inflammatory signaling cascades in various cardiac cells, thereby promoting maladaptive cardiac remodeling. Growing evidence indicates that the innate immune response pathway from the NLRP3 inflammasome, to interleukin-1 to interleukin-6, is involved in the generation of obesity-related systemic inflammation and heart failure with preserved ejection fraction. This review established the existence of obese heart failure with preserved ejection fraction based on structural and functional changes, elaborated the inflammation mechanisms of obese heart failure with preserved ejection fraction, proposed that NLRP3 inflammasome activation may play an important role in adiposity-induced inflammation, and summarized the potential therapeutic approaches.

ANGPTL3 Is Involved in the Post-prandial Response in Triglyceride-Rich Lipoproteins and HDL Components in Patients With Coronary Artery Disease.

It is well-established that there exists an inverse relationship between high-density lipoprotein (HDL) cholesterol and triglyceride (TG) levels in the plasma. However, information is lacking on the impact of post-prandial triglyceride-rich lipoproteins (TRLs) on the structure of HDL subclasses in patients with coronary artery disease (CAD). In this study, the data of 49 patients with CAD were analyzed to evaluate dynamic alterations in post-prandial lipid profiles using nuclear magnetic resonance-based methods. An enzyme-linked immunosorbent assay was used to quantify the serum angiopoietin-like protein 3 (ANGPTL3). After glucose supplementation, the expression of hepatic ANGPTL3 was evaluated both in vitro and in vivo. Compared to fasting levels, the post-prandial serum TG level of all participants was considerably increased. Although post-prandial total cholesterol in HDL (HDL-C) remained unchanged, free cholesterol in HDL particles (HDL-FC) was significantly reduced after a meal. Furthermore, the post-prandial decrease in the HDL-FC level corresponded to the increase in remnant cholesterol (RC), indicating the possible exchange of free cholesterol between HDL and TRLs after a meal. Moreover, CAD patients with exaggerated TG response to diet, defined as TG increase >30%, tend to have a greater post-prandial increase of RC and decrease of HDL-FC compared to those with TG increase ≤30%. Mechanistically, the fasting and post-prandial serum ANGPTL3 levels were significantly lower in those with TG increase ≤30% than those with TG increase >30%, suggesting that ANGPTL3, the key lipolysis regulator, may be responsible for the different post-prandial responses of TG, RC, and HDL-FC.

Clinical Profile and Prognosis of Hereditary Transthyretin Amyloid Cardiomyopathy: A Single-Center Study in South China.

Background: Hereditary transthyretin amyloid cardiomyopathy (ATTR-CM) is a genotypically heterogeneous disorder with a poor prognosis. There is limited literature describing the variants responsible for ATTRv in areas outside the United State, the United Kingdom and Europe. This study was performed to describe the clinical characteristics and genotypic profiles of this disease in South China. Methods: This was a single-center retrospective study that evaluated 29 patients with a confirmed diagnosis of hereditary transthyretin amyloid cardiomyopathy enrolled from January 2016 to November 2021. Results: 93.1% patients were male and the median age of symptom onset was 53 (46, 62.5) years old. The initial manifestations of ATTR-CM were cardiovascular symptoms (55.2%), neuropathy (41.4%) and vitreous opacity (3.4%). Phenotypes at diagnosis were mixed (82.8%), predominant cardiac (6.9%), neurological (6.9%) and ophthalmic (3.4%). Poor R-wave progression (41%), pseudo-infarct (31%) and low-voltage (31%) patterns were common findings on electrocardiogram. Unexplained increased wall thickness was observed in all 29 patients, with mean septal and posterior wall thicknesses of 14.25 ± 6.26 mm and 15.34 ± 2.84 mm, respectively. Diastolic dysfunction was also seen in all 29 patients, and 17 (58%) had a restrictive fill pattern at diagnosis. Nine different missense mutations of the TTR gene were found in 29 patients from 23 families, with c.349G>T (p.Ala117Ser) the most common mutation. The median survival time after diagnosis was 47.6 (95% CI 37.9-57.4) months, with 1, 3 and 5-year survival rates of 91.2%, 74% and 38% respectively. Patients with advanced heart failure (National Amyloidosis Staging stage II/III) had worse survival than stage I [Breslow (Generalized Wilcoxon), χ2 = 4.693, P = 0.03)]. Conclusions: ATTR amyloidosis genotypes and phenotypes are highly heterogeneous. Advanced heart failure predicts a poor prognosis. Understanding the different clinical profiles of ATTR cardiac amyloidosis with different genotype is important to its early recognition.

HDL quality features revealed by proteome‒lipidome connectivity are associated with atherosclerotic disease.

Lipoprotein, especially high-density lipoprotein (HDL), particles are composed of multiple heterogeneous subgroups containing various proteins and lipids. The molecular distribution among these subgroups is closely related to cardiovascular disease (CVD). Here, we established high-resolution proteomics and lipidomics (HiPL) methods to depict the molecular profiles across lipoprotein (Lipo-HiPL) and HDL (HDL-HiPL) subgroups by optimizing the resolution of anion-exchange chromatography and comprehensive quantification of proteins and lipids on the omics level. Furthermore, based on the Pearson correlation coefficient analysis of molecular profiles across high-resolution subgroups, we achieved the relationship of proteome‒lipidome connectivity (PLC) for lipoprotein and HDL particles. By application of these methods to high-fat, high-cholesterol diet-fed rabbits and acute coronary syndrome (ACS) patients, we uncovered the delicate dynamics of the molecular profile and reconstruction of lipoprotein and HDL particles. Of note, the PLC features revealed by the HDL-HiPL method discriminated ACS from healthy individuals better than direct proteome and lipidome quantification or PLC features revealed by the Lipo-HiPL method, suggesting their potential in ACS diagnosis. Together, we established HiPL methods to trace the dynamics of the molecular profile and PLC of lipoprotein and even HDL during the development of CVD.

Aberrant Mitochondrial Dynamics: An Emerging Pathogenic Driver of Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) is defined as a progressive segmental dilation of the abdominal aorta and is associated with high mortality. The characterized features of AAA indicate several underlying mechanisms of AAA formation and progression, including reactive oxygen species production, inflammation, and atherosclerosis. Mitochondrial functions are critical for determining cell fate, and mitochondrial dynamics, especially selective mitochondrial autophagy, which is termed as mitophagy, has emerged as an important player in the pathogenesis of several cardiovascular diseases. The PARKIN/PARIS/PGC1α pathway is associated with AAA formation and has been proposed to play a role in mitochondrial dynamics mediated by the PINK/PARKIN pathway in the pathogenesis underlying AAA. This review is aimed at deepening our understanding of AAA formation and progression, which is vital for the development of potential medical therapies for AAA.

High-sensitivity CRP may be a marker of HDL dysfunction and remodeling in patients with acute coronary syndrome.

In patients with coronary artery disease (CAD), further increasing the level of high-density lipoprotein (HDL) cholesterol (HDL-C) as an add-on to statins cannot reduce cardiovascular risk. And it has been reported that HDL functional metric-cholesterol efflux capacity (CEC) may be a better predictor of CAD risk than HDL-C. CEC measurement is time-consuming and not applicable in clinical settings. Thus, it is meaningful to explore an easily acquired index for evaluating CEC. Thirty-six CAD patients and sixty-one non-CAD controls were enrolled in this cross-sectional study. All CAD patients had acute coronary syndrome (ACS). CEC was measured using a [3H] cholesterol loading Raw 264.7 cell model with apolipoprotein B-depleted plasma (a surrogate for HDL). Proton nuclear magnetic resonance (NMR) spectroscopy was used to assess HDL components and subclass distribution. CEC was significantly impaired in CAD patients (11.9 ± 2.3%) compared to controls (13.0 ± 2.2%, p = 0.022). In control group, CEC was positively correlated with enzymatically measured HDL-C levels (r = 0.358, p = 0.006) or with NMR-determined HDL-C levels (NMR-HDL-C, r = 0.416, p = 0.001). However, in CAD group, there was no significant correlation between CEC and HDL-C (r = 0.216, p = 0.206) or NMR-HDL-C (r = 0.065, p = 0.708). Instead, we found that the level of high-sensitivity C-reactive protein (hsCRP) was inversely associated with CEC (r = - 0.351, p = 0.036). Multiple regression analysis showed that the hsCRP level was associated with CEC after adjusting other cardiovascular risk factors and HDL-C, although the association would not reach significance if adjusting for multiple testing. NMR spectroscopy showed that HDL particles shifted to larger ones in patients with high hsCRP levels, and this phenomenon was accompanied by decreased CEC. In patients with CAD, the level of HDL-C cannot reflect HDL function. The impaired correlation between HDL-C and CEC is possibly due to an inflammation-induced HDL subclass remodeling. These hypothesis-generating data suggest that hsCRP levels, a marker of acute inflammation, may associate with HDL dysfunction in ACS subjects. Due to the design limited to be correlative in nature, not permitting causal inference and a larger, strictly designed study is still needed.

New Insight Into Metformin-Induced Cholesterol-Lowering Effect Crosstalk Between Glucose and Cholesterol Homeostasis via ChREBP (Carbohydrate-Responsive Element-Binding Protein)-Mediated PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Regulation.

[Figure: see text].

Nuclear magnetic resonance reveals postprandial low-density lipoprotein cholesterol determined by enzymatic method could be a misleading indicator.

BACKGROUND: Serum concentration of low-density lipoprotein cholesterol (LDL-C) is markedly reduced after a meal. Does postprandial cholesterol in LDL truly decline via clearance of LDL particles or is there simply a redistribution of cholesterol in LDL subclasses? Thus, we sought to evaluate whether postprandial decline of LDL-C reflects a reduction of LDL particle and to assess the correlation between proprotein convertase subtilisin/kexin type 9 (PCSK9) concentration and postprandial atherogenic lipoproteins profile. METHODS: Eighty-seven persons were enrolled in this study. We measured lipid profiles by enzymatic and nuclear magnetic resonance (NMR)-based methods and serum PCSK9 concentration by enzyme-linked immunosorbent assays before and after a meal. Plasma samples were collected after a 10-h fasting and 2 and 4 h post-meal. RESULTS: Compared to the fasting status, there was significant postprandial decline of LDL-C measured enzymatically (LDL-Ce) at 2nd and 4th h [99.38 (80.43, 120.65) vs 95.51 (74.25, 117.17) vs 87.01 (69.99, 108.28) mg/dl, p < 0.000]. But there was no significant reduction in LDL particle and its cholesterol content (LDL-Cn) determined by NMR. Just the postprandial large LDL particle [186.45 (151.36, 229.42) vs 176.92 (147.43, 220.91) vs 181.77 (149.05, 224.17), p < 0.000] and its cholesterol content [19.10 (15.09, 22.37) vs 18.28 (14.59, 21.84) vs 17.79 (14.62, 22.14), p < 0.000] were greatly decreased at 2nd and 4th h compared to the fasting one. Interestingly, postprandial serum PCSK9 was decreased at 2nd and 4th h compared with fasting concentration [298.75 (233.25, 396.92) vs 257.34 (207.52, 342.36) vs 250.57 (215.02, 339.66) ng/ml, p < 0.000]. The postprandial percent decrease in serum PCSK9 at 4th h was positively correlated to the percent decline in postprandial LDL-Ce (r = 0.252, p = 0.019) but was independently associated with the percent increase in remnant cholesterol (r = 0.262, p = 0.016). CONCLUSIONS: Postprandial decline of LDL-C determined enzymatically was not confirmed by NMR-based methods. Indeed, there exists cholesterol redistribution in LDL subclasses following a meal. The decrease of postprandial PCSK9 may be secondary to the increase in intrahepatic lipids following food intake.

Synthetic high-density lipoproteins delivering liver X receptor agonist prevent atherogenesis by enhancing reverse cholesterol transport.

Liver X nuclear receptor (LXR) agonists are promising anti-atherosclerotic agents that increase the expression of cholesterol transporters on atheroma macrophages leading to increased efflux of cholesterol to endogenous high-density lipoprotein (HDL) acceptors. HDL subsequently delivers effluxed cholesterol to the liver by the process of reverse cholesterol transport, resulting in reduction of atherosclerotic plaques. However, LXR agonists administration triggers undesirable liver steatosis and hypertriglyceridemia due to increased fatty acid and sterol synthesis. LXR-induced liver toxicity, poor drug aqueous solubility and low levels of endogenous HDL acceptors in target patient populations limit the clinical translation of LXR agonists. Here, we propose a dual-antiatherogenic strategy for administration of the LXR agonist, T0901317 (T1317), by encapsulating in synthetic HDL (sHDL) nanoparticles. sHDL had been clinically proven to serve as cholesterol acceptors, resulting in plaque reduction in atherosclerosis patients. In addition, the hydrophobic core and endogenous atheroma-targeting ability of sHDL allow for encapsulation of water-insoluble drugs and their subsequent delivery to atheroma. Several compositions of sHDL were tested to optimize both T1317 encapsulation efficiency and ability of T1317-sHDL to efflux cholesterol. Optimized T1317-sHDL exhibited more efficient cholesterol efflux from macrophages and enhanced atheroma-targeting relative to free drug. Most importantly, in an apolipoprotein E deficient (ApoE-/-) atherosclerosis progression murine model, T1317-sHDL showed superior inhibition of atherogenesis and reduced hypertriglyceridemia side effects in comparison to the free drug and blank sHDL. The T1317-sHDL pharmacological efficacy was observed at doses lower than those previously described for LXR agents, which may have additional safety benefits. In addition, the established clinical manufacturing, safety and efficacy of blank sHDL nanoparticles used in this study could facilitate future clinical translation of LXR-loaded sHDLs.

Association between Cardiovascular Burden and Requirement of Intensive Care among Patients with Mild COVID-19.

BACKGROUND: Information regarding the impact of cardiovascular (CV) conditions on disease progression among patients with mild coronavirus disease 2019 (COVID-19) is limited. METHODS: This study evaluated the association of underlying CV conditions with disease progression in patients with mild COVID-19. The primary outcome was the need to be transferred to the designated hospital for intensive care due to COVID-19 disease progression. The patients were divided into with and without CV conditions as well as stable and intensive care groups. RESULTS: Of the 332 patients with mild COVID-19, the median age was 51 years (IQR, 40-59 years), and 200 (61.2%) were female. Of the 48 (14.5%) patients with CV conditions, 23 (47.9%) progressed to severe disease status and required intensive care. Compared with patients without CV conditions, patients with CV conditions were older and more likely to have fatigue, chest tightness, and myalgia. The rate of requiring intensive care was significantly higher among patients with CV conditions than in patients without CV conditions (47.92% vs. 12.4%; P < 0.001). In subgroup analysis, the rate of requiring intensive care was also higher among patients with either hypertension or coronary heart disease (CHD) than in patients without hypertension or CHD. The multivariable regression model showed that CV condition served as an independent risk factor for intensive care (odds ratio (OR), 2.652 (95% CI, 1.019-6.899)) after adjustment for various cofounders. CONCLUSIONS: Patients with mild COVID-19 complicating CV conditions are susceptible to develop severe disease status and requirement for intensive care.

Intraventricular muscle bundle as a novel cause of left ventricular aneurysm.

BACKGROUND: There are a variety of causes of left ventricular aneurysm, but it is rarely due to a disturbance in intraventricular hemodynamics. To the best of our knowledge, there have been no reports of ventricular aneurysm at the left ventricular apex caused by an abnormal left ventricular muscle bundle. CASE PRESENTATION: We report two cases of patients with congenital abnormal left ventricular muscle bundles which caused disturbances in intraventricular hemodynamics. This process eventually led to a left ventricular aneurysm at the apex of the heart. In both cases, transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) indicated ventricular aneurysm formation at the apex of the left ventricle. There were also abnormal muscular bundles connecting the ventricular septum and the posterior wall of the left ventricle. The only differences between these two cases were the comorbidities and severity of symptoms. CONCLUSION: Ventricular aneurysm at the apex of the left ventricle is common. However, it is rare for a ventricular aneurysm to form due to intraventricular hemodynamic disturbances caused by an abnormal muscle bundle as opposed to that due to original ventricular wall damage, which is more common. There is currently a lack of relevant studies on the treatment and prognosis of such patients. Whether surgical resection of a ventricular aneurysm leads to a better prognosis remains uncertain.

Evaluation of variation in D-dimer levels among COVID-19 and bacterial pneumonia: a retrospective analysis.

In the recent outbreak of novel coronavirus infection worldwide, the risk of thrombosis and bleeding should be concerned. We aimed to observe the dynamic changes of D-dimer levels during disease progression to evaluate their value for thrombosis. In this study, we report the clinical and laboratory results of 57 patients with confirmed COVID-19 pneumonia and 46 patients with confirmed community-acquired bacterial pneumonia (CAP). And their concentrations of D-dimer, infection-related biomarkers, and conventional coagulation were retrospectively analyzed. The Padua prediction score is used to identify patients at high risk for venous thromboembolism (VTE). The results found that, on admission, both in COVID-19 patients and CAP patients, D-dimer levels were significantly increased, and compared with CAP patients, D-dimer levels were higher in COVID-19 patients (P < 0.05). Besides, we found that in COVID-19 patients, D-dimer were related with markers of inflammation, especially with hsCRP (R = 0.426, P < 0.05). However, there was low correlation between VTE score and D-dimer levels (Spearman's R = 0.264, P > 0.05) weakened the role of D-dimer in the prediction of thrombosis. After treatments, D-dimer levels decreased which was synchronous with hsCRP levels in patients with good clinical prognosis, but there were still some patients with anomalous increasing D-dimer levels after therapy. In conclusion, elevated baseline D-dimer levels are associated with inflammation but not with VTE score in COVID-19 patients, suggesting that it is unreasonable to judge whether anticoagulation is needed only according to D-dimer levels. However, the abnormal changes of D-dimer and inflammatory factors suggest that anticoagulant therapy might be needed.

Comparison of calculated remnant lipoprotein cholesterol levels with levels directly measured by nuclear magnetic resonance.

BACKGROUND: Remnant cholesterol (RC) can partly explain the residual risk in atherosclerotic cardiovascular disease (ASCVD). A consensus method of measuring RC levels has not been established yet. In clinical practice, RC levels are usually calculated from the standard lipid profile, which are not true RC. Nuclear magnetic resonance (NMR) can measure RC levels directly. This study aimed to characterize RC at fasting and non-fasting states in more details and establish the performance of calculated RC and NMR-measured RC. METHODS: Blood samples at fasting state and at 2 h and 4 h postprandial states were collected in 98 subjects. Lipid parameters including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), subfractions 3, 4, and 5 of very low-density lipoprotein cholesterol (VLDL3-C, VLDL4-C, and VLDL5-C, respectively), and intermediate-density lipoprotein cholesterol (IDL-C) were measured by enzymatic method and NMR. RC levels calculated from the standard lipid profile or measured by NMR were referred here as RCe or RCn. RESULTS: The RCe and RCn levels were different, but both of them increased after a meal (P < 0.05), especially at 4 h postprandial state. Low correlations were found between RCe and RCn in the 1st, 2nd, and 3rd quartiles of TG, but RCn showed great correlation with RCe in the highest quartile regardless of the fasting or non-fasting state (R = 0.611, 0.536, and 0.535 for 0 h, 2 h, and 4 h, respectively). However, across the 2nd and 3rd quartiles, RCe levels were nearly close to RCn levels. RCe levels tended to overestimate RCn levels in the 1st quartile of TGe levels with median differences of 0.23(- 0.13, 0.63) and underestimate RCn levels with median differences of - 0.23(- 0.33, 0.07) in the highest quartile of TGe levels. CONCLUSIONS: RC calculated from the standard lipid profile as TC minus LDL-C minus HDL-C is different from the NMR-measured RC. According to different TG levels, RC could overestimate or underestimate the actual RC level. Developing a consensus clinical method to measure RC levels is necessary, so that results from different studies and platforms can be more directly compared. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900020873. Registered in 21 January 2019 - Retrospectively registered.

HDL-associated apoCIII plays an independent role in predicting postprandial hypertriglyceridemia.

BACKGROUND: The mechanism for an abnormal pattern of triglyceride (TG) metabolism in response to a meal still needs further investigation. Extensive pieces of evidence have shown that apolipoprotein CIII (apoCIII) is a critical modulator of plasma TG metabolism mostly by inhibiting the hydrolysis of TG. Little is known about the role of apoCIII contained in high density lipoprotein (HDL) in plasma TG metabolism after a meal. METHODS: Fasting and 4-hour postprandial peripheral venous blood were collected in 91 subjects selected from our hospital. Serum lipid parameters, apoCIII levels and HDL subcomponents were tested by standard laboratory procedures, ELISA, and nuclear magnetic resonance (NMR), respectively. The t-test, and Non-parametric tests were performed to examine differences between groups, Pearson's correlation and multiple regression analysis were used to assess the correlations between apoCIII (HDL-associated or nonHDL-associated) and postprandial TG. RESULTS: There was a significant increase in TG after a meal compared to fasting status [155.40(96.70-251.07) mg/dl.vs.118.53(83.38-173.29)mg/dl, p < 0.001]. However, the total apoCIII levels were unchanged before (11.56(7.89-16.22) mg/dl) and after a meal (11.66(7.75-16.02)mg/dl, p = 0.124), while a significant increase in HDL-associated apoCIII (HDL-apoCIII) was observed from fasting (5.25(3.92-7.83)mg/dl) to post-meal (6.46(4.57-8.76)mg/dl, p = 0.001). Unlike nonHDL-apoCIII, HDL-apoCIII was positively correlated with both fasting and postprandial plasma TG in subjects with baseline plasma TG > 118.53 mg/dl (R = 0.503, p < 0.001 for fasting, R = 0.584, p < 0.001 for postprandial). Besides, in the subjects who had an abnormal TG response to a meal, which was defined as postprandial plasma TG increase of>30% compared to baseline TG levels, postprandial HDL-apoCIII was also increased significantly [5.37(3.52-7.02)mg/dl.vs.6.64(4.61-8.86)mg/dl, p = 0.001]. The enrichment of apoCIII in HDL led to changes of TG, cholesterol, free cholesterol, phospholipid and apoAII contents in HDL particles defined by NMR. CONCLUSION: Enrichment of apoCIII in HDL particles potentially plays an independent role in postprandial hypertriglyceridemia.