Abstract P428: A New Mouse Model Of Myocardial Lipids, Fibrosis, Arrhythmia And Diastolic Dysfunction Induced By Hyperlipidemia And Cardiac LDLR

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Monique Williams ◽  
Camila Iansen Irion ◽  
Jose Manuel Condor Capcha ◽  
Guerline Lambert ◽  
Grace Seo ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Cardiac Function ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Lipid Accumulation ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Poloxamer 407 ◽  
Whole Body ◽  
Subsequent Increase

Background: Hyperlipidemia is a major risk factor for CVD. Patients with HF with preserved ejection fraction (HFpEF) have more myocardial lipid accumulation than patients with reduced EF (HFrEF). RNASeq data from cardiac biopsies showed downregulation of the gene for lipoprotein lipase (LPL) that degrades triglycerides, in HFpEF patients compared to healthy and HFrEF controls. Poloxamer-407 (p407) induces hyperlipidemia by blocking LPL and subsequent increase in plasma triglycerides and low-density lipoprotein (LDL) cholesterol. We hypothesized that mice treated with p407 and cardiac LDL-Receptor (LDLR) over-expression (OE) develop hyperlipidemia, myocardial lipid accumulation, and diastolic dysfunction resulting in HFpEF and arrhythmias. Methods: Baseline cardiac function was assessed by echo for male and female C57Bl6 mice (n=9) for 2 groups: 4wk biweekly i.p. p407-injections with (n=4) or without (n=3) single i.v. injection with AAV9-cTnT-LDLR. Cardiac function was assessed by echocardiography at 3 and 4 wks. Blood Pressure (BP) and Whole Body Plethysmography (WBP) were assessed during wk4. Ttest was used for statistics. PR and ORO staining and telemetry were performed at wk4. Results: At wk3, P407 and LDLR OE led to alterations in diastolic function (increased IVCT, IVRT, MV E/E’, MPI, and NFT) and increased LV wall thickness, p<0.05. At wk4, there was pulmonary hypertension (increased mean pulmonary arterial pressure, decreased pulmonary acceleration time p <.05).Histology showed excessive myocardial lipids and fibrosis, and telemetry showed incidents of second-degree and higher-degree AV block. The group injected solely with p407 show e d alterations in diastolic function (increased IVCT, IVRT, NFT, LVMPI, LVMPI NFT p<.05 ) and decreased EDV, ESV, EDLVM, ESLVM, p<.05 at wk4. All groups had preserved %EF and no abnormalities in BP or WBP. Conclusions: P407 and cardiac LDLR OE induce a drastic decline in cardiac diastolic function over a shorter period of time compared to p407 alone. Diastolic dysfunction was observed in wk3 followed by pulmonary hypertension, arrhythmia, myocardial lipid accumulation and fibrosis in wk4. This new model may allow for more rapid investigations of cardiac abnormalities seen in HFpEF patients.

scholarly journals Evolution of cardiac function in COVID 19 patients in the intensive care unit: insights from machine learning

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
P Marti Castellote ◽  
F Loncaric ◽  
M Nogueira ◽  
M Sitges ◽  
B Stessel ◽  
...  
Keyword(s):  
Machine Learning ◽  
Pulmonary Hypertension ◽  
Intensive Care ◽  
Cardiac Function ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Clinical Data ◽  
Cardiac Cycle ◽  
Doppler Velocity ◽  
Output Space

Abstract Funding Acknowledgements Type of funding sources: None. Background Repeated echocardiographic assessment of cardiac function is integral in management of intensive care units (ICU) patients. Machine learning (ML) can assist by integrating whole-cardiac cycle echo data derived from flow assessment and deformation imaging, and grouping patients on the basis of patterns of cardiac dysfunction and its evolution over time. Cardiac involvement has been suggested to be important in COVID-19 outcome and echo evaluation can inform on cardiac status. We use unsupervised ML to investigate and integrate longitudinal data from the COVID-HO study (NCT04371679) to determine the potential of tracking changes in cardiac function during ICU hospitalization.  Methods In a single-centre, COVID-19 patients (n = 38) were prospectively followed with echocardiography as part of ICU management. The endpoint was defined as death or ICU discharge. LV myocardial deformation, as well as aortic, mitral and pulmonary artery blood-pool Doppler velocity profiles were used as input for ML. Clinical data was used to validate the ML derived phenotypes. Echo data from the initial and final echo examination were used to create an output space where participants were positioned based on cardiac function blinded to outcome status. Regression was used to estimate the echo and clinical characteristics of different regions in the space. Patient trajectories in the output space were investigated for each patient. Results Endpoint was not reached in 24% (n = 9) at the time of analysis. The cohort was 68% male, aged 65 ± 12 years, and with an ICU mortality 21% (n = 8). The median spent in ICU was 10 (IQR 7-18) days. The ML analysis demonstrated a heterogeneous output space (Fig 1A) we could define a gradual change in the shape of the pulmonary outflow velocity profile, from a normal  towards pulmonary hypertension (Fig 1A, x axis). Jointly with differences in diastolic function (mitral inflow fusion and A wave accentuation) defined two regions: with signs of pulmonary hypertension (gray); and with normal pulmonary pressures but LV diastolic dysfunction (yellow). Investigation of patient trajectories (Fig 1B) demonstrated the feasibility of tracking changes during ICU hospitalization, showing a shift of a patient that died in the ICU, from initial diastolic dysfunction towards pulmonary hypertension (red), and a patient shifting from a region with normal diastolic function towards pulmonary hypertension, but with a positive outcome (blue). Echo data concurs with observed dynamics (Fig 1C and 1D). Conclusion ML can integrate complex, whole-cardiac cycle echo data to group heterogeneous patients based on similarity of cardiac function. Patient trajectories across the output space demonstrate the feasibility of ML for echo data-based follow-up of patients during ICU hospitalization. Further echo and clinical data integration can improve characterisation of the output space regions and better define changes in cardiac function during hospitalization. Abstract Figure 1

scholarly journals BLOS1 mediates kinesin switch during endosomal recycling of LDL receptor

2020 ◽  
Author(s):  
Chang Zhang ◽  
Chanjuan Hao ◽  
Guanghou Shui ◽  
Wei Li
Keyword(s):  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Cholesterol Homeostasis ◽  
Whole Body ◽  
Cellular Mechanisms ◽  
Anterograde Transport ◽  
Recycling Endosomes ◽  
Endosomal Recycling ◽  
Density Lipoprotein Receptor

AbstractLow-density lipoprotein receptor (LDLR) in hepatocytes plays a key role in normal clearance of circulating LDL and in whole body cholesterol homeostasis. The trafficking of LDLR is highly regulated in clathrin-dependent endocytosis, endosomal recycling and lysosomal degradation. Current studies have been focusing on its endocytosis and degradation. However, the detailed molecular and cellular mechanisms underlying its endosomal recycling are largely unknown. We found that BLOS1, a shared subunit of BLOC-1 and BORC, is involved in LDLR endosomal recycling. Loss of BLOS1 leads to less membrane LDLR and impairs LDL clearance from plasma in hepatocyte-specific BLOS1 knockout mice. BLOS1 interacts with kinesin-3, and that BLOS1 acts as a new adaptor for kinesin-2 to coordinate kinesin-3 and kinesin-2 during the long-range transport of recycling endosomes (REs) to plasma membrane along microtubule tracks to overcome hurdles at microtubule intersections. These findings provide new insights into RE’s anterograde transport and the pathogenesis of dyslipidemia.

Assessing the Validity of Echocardiographic Criteria for Left Ventricular Diastolic Dysfunction in Patients with Pulmonary Hypertension

Cardiology ◽  
2020 ◽  
Vol 145 (11) ◽  
pp. 703-709
Author(s):  
John David Allison ◽  
Carl Zehner ◽  
Xiaoming Jia ◽  
Ihab Rafic Hamzeh ◽  
Mahboob Alam ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Heart Catheterization ◽  
Mitral Inflow ◽  
Mitral Annular Velocity ◽  
Lv Diastolic Dysfunction ◽  
Lv Diastolic Function

<b><i>Background:</i></b> In patients with pulmonary hypertension (PHT), the assessment of left ventricular (LV) diastolic function by echocardiography may not be reliable. PHT can affect Doppler parameters of LV diastolic function such as mitral inflow velocities and mitral annular velocities. The current guidelines for the assessment of LV diastolic function do not recommend specific adjustments for patients with PHT. <b><i>Methods:</i></b> We analyzed 36 patients from the PHT clinic that had an echocardiogram and right heart catheterization performed within 6 months of each other. Early mitral inflow velocity (E), lateral mitral annular velocity (lateral e’), septal mitral annular velocity (septal e’), tricuspid free wall annular velocity (RV e’) were measured and compared to the invasively measured intracardiac pressures including pulmonary capillary wedge pressure (PCWP), mean pulmonary artery pressure, and right ventricular end-diastolic pressure. <b><i>Results:</i></b> Among patients with PHT, the specificity of the septal e’ for LV diastolic dysfunction was 0.19, and the positive predictive value was 0.13 (lower than the lateral e’ or E/average e’). By receiver-operating characteristic curve analysis, the area under the curve (AUC) of lateral and septal e’ was just 0.64 (<i>p</i> = 0.9) and 0.53 (<i>p</i> = 0.6), respectively, while the AUC of average E/e’ was 0.94 (<i>p</i> &#x3c; 0.001). The septal e’ was paradoxically lower at 6.5 ± 1.9 cm/s for normal PCWP compared to 6.9 ± 1.7 cm/s for elevated PCWP (<i>p</i> = 0.04). 81 versus 40% (<i>p</i> = 0.017) of patients with normal versus elevated PCWP had an abnormal septal e’ &#x3c;7 cm/s. By linear regression, there was no correlation between the Doppler parameters of LV diastolic function and the PCWP. <b><i>Conclusion:</i></b> Our study suggests E/average e’ may be the only reliable tissue Doppler parameter of LV diastolic dysfunction in patients with PHT, and that septal e’ is paradoxically decreased in patients with PHT and normal left-sided filling pressures.

scholarly journals A dual apolipoprotein C-II mimetic–apolipoprotein C-III antagonist peptide lowers plasma triglycerides

2020 ◽  
Vol 12 (528) ◽  
pp. eaaw7905 ◽  
Author(s):  
Anna Wolska ◽  
Larry Lo ◽  
Denis O. Sviridov ◽  
Mohsen Pourmousa ◽  
Milton Pryor ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
Ex Vivo ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Dynamics Simulation ◽  
Whole Body ◽  
High Density Lipoproteins ◽  
Apolipoprotein C

Recent genetic studies have established that hypertriglyceridemia (HTG) is causally related to cardiovascular disease, making it an active area for drug development. We describe a strategy for lowering triglycerides (TGs) with an apolipoprotein C-II (apoC-II) mimetic peptide called D6PV that activates lipoprotein lipase (LPL), the main plasma TG-hydrolyzing enzyme, and antagonizes the TG-raising effect of apoC-III. The design of D6PV was motivated by a combination of all-atom molecular dynamics simulation of apoC-II on the Anton 2 supercomputer, structural prediction programs, and biophysical techniques. Efficacy of D6PV was assessed ex vivo in human HTG plasma and was found to be more potent than full-length apoC-II in activating LPL. D6PV markedly lowered TG by more than 80% within a few hours in both apoC-II–deficient mice and hAPOC3-transgenic (Tg) mice. In hAPOC3-Tg mice, D6PV treatment reduced plasma apoC-III by 80% and apoB by 65%. Furthermore, low-density lipoprotein (LDL) cholesterol did not accumulate but rather was decreased by 10% when hAPOC3-Tg mice lacking the LDL-receptor (hAPOC3-Tg × Ldlr−/−) were treated with the peptide. D6PV lowered TG by 50% in whole-body inducible Lpl knockout (iLpl−/−) mice, confirming that it can also act independently of LPL. D6PV displayed good subcutaneous bioavailability of about 80% in nonhuman primates. Because it binds to high-density lipoproteins, which serve as a long-term reservoir, it also has an extended terminal half-life (42 to 50 hours) in nonhuman primates. In summary, D6PV decreases plasma TG by acting as a dual apoC-II mimetic and apoC-III antagonist, thereby demonstrating its potential as a treatment for HTG.

scholarly journals Impact of Left Ventricular Diastolic Dysfunction and Biomarkers on Pulmonary Hypertension in Patients with Severe Aortic Stenosis

Medicina ◽  
2018 ◽  
Vol 54 (4) ◽  
pp. 63
Author(s):  
Birutė Gumauskienė ◽  
Aušra Krivickienė ◽  
Regina Jonkaitienė ◽  
Jolanta Vaškelytė ◽  
Adakrius Siudikas ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Aortic Valve ◽  
Aortic Stenosis ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Severe Aortic Stenosis ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Ventricular Diastolic Dysfunction ◽  
Lv Diastolic Dysfunction

Background: Severe aortic stenosis (AS) complicated by pulmonary hypertension (PH) is associated with poor outcomes after surgical aortic valve replacement (AVR). There is still scarce information about predictors of secondary PH in this group of patients. Objectives: The aim of this study was to investigate the prognostic impact of biomarkers together with conventional Doppler echocardiographic parameters of left ventricular diastolic function on elevated pulmonary systolic pressure (PSP) in severe AS patients before surgical AVR. Methods: Sixty patients with severe isolated AS (aortic valve area <1 cm2) underwent echocardiography, N-terminal pro B-type natriuretic peptide (NT-proBNP) and growth differentiation factor-15 (GDF-15) measurements before AVR. PSP, left ventricular ejection fraction (LV EF), parameters of LV diastolic function (E/E’ ratio, mitral valve deceleration time (MV DT) and left atrial (LA) volume) were evaluated. PH was defined as an estimated PSP ≥ 45 mmHg. Results: Of the 60 patients, 21.7% with severe isolated AS had PH with PSP ≥ 45 mmHg (58.5 ± 11.2 mmHg). LV EF did not differ between groups and was not related to an elevated PSP (50 ± 8 vs. 49 ± 8%, p = 0.58). Parameters of LV diastolic dysfunction (E/E’ ratio > 14 (OR 6.00; 95% CI, 1.41–25.48; p = 0.009), MV DT ≤ 177.5 ms (OR 9.31; 95% CI, 2.06–41.14; p = 0.001), LA volume > 100 mL (OR 9.70; 95% CI, 1.92–49.03; p = 0.002)) and biomarkers (NT-proBNP > 4060 ng/L (OR 12.54; 95% CI, 2.80–55.99; p < 0.001) and GDF-15 > 3393 pg/mL (OR 18.33; 95% CI, 2.39–140.39; p = 0.001)) were significantly associated with elevated PSP in severe AS. Conclusions: Left ventricular diastolic dysfunction and elevated biomarkers levels could predict the development of pulmonary hypertension in patients with severe aortic stenosis. Elevation of biomarkers paired with worsening of LV diastolic dysfunction could help to stratify patients for earlier surgical treatment before the development of pulmonary hypertension.

scholarly journals Validation of the 2016 ASE/EACVI Guideline for Diastolic Dysfunction in Patients With Unexplained Dyspnea and a Preserved Left Ventricular Ejection Fraction

2021 ◽  
Author(s):  
Arno A. van de Bovenkamp ◽  
Vidya Enait ◽  
Frances S. de Man ◽  
Frank T. P. Oosterveer ◽  
Harm Jan Bogaard ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Diagnostic Performance ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction

Background Echocardiography is considered the cornerstone of the diagnostic workup of heart failure with preserved ejection fraction. Thus far, validation of the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) echo‐algorithm for evaluation of diastolic (dys)function in a patient suspected of heart failure with preserved ejection fraction has been limited. Methods and Results The diagnostic performance of the 2016 ASE/EACVI algorithm was assessed in 204 patients evaluated for unexplained dyspnea or pulmonary hypertension with echocardiogram and right heart catheterization. Invasively measured pulmonary capillary wedge pressure (PCWP) was used as the gold standard. In addition, the diagnostic performance of H 2 FPEF score and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) were evaluated. There was a poor correlation between indexed left atrial volume, E/e′ (septal and average) or early mitral inflow (E), and PCWP ( r =0.25–0.30, P values all <0.01). No correlation was found in our cohort between e′ (septal or lateral) or tricuspid valve regurgitation and PCWP. The correlation between diastolic function grades of the ASE/EACVI algorithm and PCWP was poor ( r =0.17, P <0.05). The ASE/EACVI algorithm had a sensitivity and specificity of 35% and 87%, respectively; an accuracy of 67% and an area under the curve of 0.56. Moreover, in 30% of cases the algorithm was not applicable or indeterminate. H 2 FPEF score had a modest correlation with PCWP ( r =0.44, P <0.0001), and accuracy was 73%; NT‐proBNP correlated weakly with PCWP ( r =0.24, P <0.001), and accuracy was 57%. Conclusions The 2016 ASE/EACVI algorithm for the assessment of diastolic function has a limited diagnostic accuracy in patients evaluated for unexplained dyspnea and/or pulmonary hypertension, and especially sensitivity to detect diastolic dysfunction was low.

scholarly journals HDL-C to hsCRP ratio is associated with left ventricular diastolic function in absence of significant coronary atherosclerosis

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Lufan Sun ◽  
Xiaorui Liu ◽  
Wenna Li ◽  
Dalin Jia
Keyword(s):  
Regression Analysis ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Coronary Atherosclerosis ◽  
Protective Factor ◽  
Density Lipoprotein ◽  
Left Ventricular Diastolic Function ◽  
Left Ventricular ◽  
Lv Diastolic Dysfunction ◽  
Lv Diastolic Function

Abstract Background High-density lipoprotein cholesterol (HDL-C) is considered as a protective marker of coronary atherosclerotic disease (CAD). It is still not clear if HDL-C is associated with left ventricular (LV) diastolic function in an inflammation-related manner in absence of significant coronary atherosclerosis. Methods 392 patients who complained of chest pain and were suspected of CAD without heart failure were enrolled in this study. Coronary angiography or coronary artery CT scan was performed to detect coronary atherosclerosis. Transthoracic echocardiography was performed to evaluate cardiac function. Plasma level of HDL-C and high-sensitive C-reactive protein (hsCRP) were determined in each subject. Relationship between HDL-C/hsCRP ratio and LV diastolic function in subjects without significant coronary atherosclerosis was investigated. Results 204 subjects without significant coronary plaques were analyzed finally, including 84 males and 120 females whose ages ranged from 30 to 84 years old. When divided into HDL-C/hsCRP quartiles, those in the fourth quartile demonstrated the best diastolic function (E/e’ 10.14 ± 2.87, P = 0.02 ). HDL-C/hsCRP was the most significant factor correlated with E/e’ in univariate regression analysis (r = − 0.232, P < 0.001) and multiple regression analysis adjusted by other factors (standardized β = − 0.258 , P < 0.0005 ). In logistic regression, HDL-C/hsCRP was proved to be a protective factor of LV diastolic dysfunction E/e’ > 14 (OR = 0.649, 95%CI 0.444–0.948,P = 0.025 ). The sensitivity and specificity of using HDL-C/hsCRP < 0.98 to predict LV diastolic dysfunction were 64.3% and 56.2%, respectively. HDL-C/hsCRP ratio presented a reduced trend as increasing rate of CV risk factors. Conclusions HDL-C/hsCRP ratio strongly correlates with LV diastolic function in absence of significant coronary atherosclerosis. Low HDL-C/hsCRP ratio tends to relate with LV diastolic dysfunction.

Diastolic Dysfunction Is an Independent Risk Factor for Death in Patients with Sickle Cell Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 206-206 ◽  
Author(s):  
Vandana Sachdev ◽  
Roberto F. Machado ◽  
Yukitaka Shizukudu ◽  
Yesoda Rao ◽  
Stanislav Sidenko ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Pulmonary Artery ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Sickle Cell ◽  
Systolic Pressure ◽  
Pulmonary Artery Systolic Pressure ◽  
Cell Disease

Abstract Background. Pulmonary hypertension, defined by an elevated pulmonary artery systolic pressure measured by Doppler-echocardiogram, has been identified as the major predictor of death in the adult sickle cell disease population. While diastolic dysfunction is also observed in this population, the prevalence in unselected patients, the association with high pulmonary artery systolic pressure, and the attributable mortality remain unknown. Methods. Diastolic function parameters, pulmonary artery systolic pressures and right and left ventricular size and function were measured prospectively in 215 subjects with sickle cell disease. Associations between these parameters, lab and echocardiographic variables and prospective mortality were determined. Results. Diastolic dysfunction, measured by conventional and tissue-Doppler echocardiography, was present in 19% of patients with sickle cell disease. Diastolic dysfunction and pulmonary hypertension were both present in approximately 11% of patients and diastolic dysfunction accounted for approximately 10–20% of the variability in tricuspid regurgitant jet velocity. Importantly, Cox Proportional Hazards analysis revealed that diastolic dysfunction, as reflected by low E/A ratio, was associated with prospective mortality with a risk ratio of 1.9 (95%CI 1.0 to 3.7; p=0.028), even after adjustment for tricuspid regurgitant jet velocity. While pulmonary hypertension remained the dominant determinant of mortality risk, even after adjustment for measures of diastolic function (adjusted rate ratio of 5.3; 95% CI= 1.9 to15.0; p<0.001), the risk was additive such that patients with both risk factors had an odds ratio for death of 10.1 (95% CI= 3.2 to 31.9; p<0.001). Conclusions. Diastolic dysfunction and pulmonary hypertension due to other causes each contribute independently to prospective mortality in patients with sickle cell disease. Patients with both risk factors have an extremely poor prognosis. These data support the implementation of Doppler-echocardiographic screening of adult patients with sickle cell disease to identify individuals at high risk of death for intensified therapy. Figure Figure

scholarly journals BLOS1 mediates kinesin switch during endosomal recycling of LDL receptor

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Chang Zhang ◽  
Chanjuan Hao ◽  
Guanghou Shui ◽  
Wei Li
Keyword(s):  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Cholesterol Homeostasis ◽  
Whole Body ◽  
Cellular Mechanisms ◽  
Anterograde Transport ◽  
Recycling Endosomes ◽  
Endosomal Recycling ◽  
Density Lipoprotein Receptor

Low-density lipoprotein receptor (LDLR) in hepatocytes plays a key role in plasma clearance of circulating LDL and in whole body cholesterol homeostasis. The trafficking of LDLR is highly regulated in clathrin-dependent endocytosis, endosomal recycling and lysosomal degradation. Current studies focus on its endocytosis and degradation. However, the detailed molecular and cellular mechanisms underlying its endosomal recycling are largely unknown. We found that BLOS1, a shared subunit of BLOC-1 and BORC, is involved in LDLR endosomal recycling. Loss of BLOS1 leads to less membrane LDLR and impairs LDL clearance from plasma in hepatocyte-specific BLOS1 knockout mice. BLOS1 interacts with kinesin-3 motor KIF13A, and BLOS1 acts as a new adaptor for kinesin-2 motor KIF3 to coordinate kinesin-3 and kinesin-2 during the long-range transport of recycling endosomes (REs) to plasma membrane along microtubule tracks to overcome hurdles at microtubule intersections. This provides new insights into RE’s anterograde transport and the pathogenesis of dyslipidemia.

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