Journal: International Journal of Cardiology. Cardiovascular Risk and Prevention

Article Title: Effects of PCSK9 inhibitors on vascular function, lipid profile, and cardiovascular outcomes in patients with peripheral artery disease: A systematic review and meta-analysis

doi: 10.1016/j.ijcrp.2026.200590

Figure Lengend Snippet: Summary of included studies.

Article Snippet: Clavijoa, 2023 , RCT, Double-blind , USA , 6 months , Evolocumab 420 mg SC q4w , placebo , 35 , 35 , 70 , Patients aged 40–85 years with a diagnosis of atherosclerotic cardiovascular disease and PAD (Rutherford class I-VI), confirmed by an ankle-brachial index (ABI) ≤0.9 at rest or ≤0.8 after exercise, angiography, duplex ultrasound, or a history of lower extremity surgical or endovascular revascularization. Patients had to be at least one month from their most recent intervention, stable on maximal tolerated lipid-lowering therapy for at least four weeks, and have a fasting LDL cholesterol ≥55 mg/dL or non-HDL cholesterol ≥80 mg/dL. , MWT at 6 months , After six months, Evolocumab significantly improved MWT, FMD, Carotid IMT, and plasma MRP-14 levels. In contrast, changes in pain-free walking time, ABI, TBI, transcutaneous oxygen pressure, oxLDL, and sCD36 were not statistically significant..

Techniques: Control, Biomarker Discovery, Clinical Proteomics, Activation Assay

Journal: International Journal of Cardiology. Cardiovascular Risk and Prevention

Article Title: Effects of PCSK9 inhibitors on vascular function, lipid profile, and cardiovascular outcomes in patients with peripheral artery disease: A systematic review and meta-analysis

doi: 10.1016/j.ijcrp.2026.200590

Figure Lengend Snippet: Summary of included studies.

Article Snippet: Clavijoa, 2023 , RCT, Double-blind , USA , 6 months , Evolocumab 420 mg SC q4w , placebo , 35 , 35 , 70 , Patients aged 40–85 years with a diagnosis of atherosclerotic cardiovascular disease and PAD (Rutherford class I-VI), confirmed by an ankle-brachial index (ABI) ≤0.9 at rest or ≤0.8 after exercise, angiography, duplex ultrasound, or a history of lower extremity surgical or endovascular revascularization. Patients had to be at least one month from their most recent intervention, stable on maximal tolerated lipid-lowering therapy for at least four weeks, and have a fasting LDL cholesterol ≥55 mg/dL or non-HDL cholesterol ≥80 mg/dL. , MWT at 6 months , After six months, Evolocumab significantly improved MWT, FMD, Carotid IMT, and plasma MRP-14 levels. In contrast, changes in pain-free walking time, ABI, TBI, transcutaneous oxygen pressure, oxLDL, and sCD36 were not statistically significant..

Techniques: Control, Biomarker Discovery, Clinical Proteomics, Activation Assay

Journal: The Journal of Biological Chemistry

Article Title: Cell type-specific control of cardiometabolic disease by the dileucine motif of the LDL receptor-related protein LRP1

doi: 10.1016/j.jbc.2026.111421

Figure Lengend Snippet: Hepatosteatosis and liver gene expression in Western diet-fed Lrp1 LL Ldlr −/− (LL) and Lrp1 AA Ldlr −/− (AA) mice. Age-matched LL and AA mice were fed Western diet for 16 weeks. A , livers were obtained from 7 LL and 6 AA mice for histological examination of steatosis and measurements of triglyceride and cholesterol content. Total RNA was extracted from 6 to 7 LL and 6 to 7 AA mice for RT-PCR to quantify expression of: ( B ) cholesterol synthesis genes HMGCR, HMGCS, and SREBP2, ( C ) fatty acid oxidation genes ACOX1, CYPT1α, and PDK4, and ( D ) PPARα, PPARβ, and PPARγ. The data were evaluated for statistical significance by Student’s t test with p values as shown. E , protein levels of PPARα, PPARβ/δ, and PPARγ in livers prepared from Western diet-fed LL and AA mice were assessed by Western blot analysis of liver lysates using GAPDH as loading control. The data were normalized to the mean levels of expression in LL samples, with fold changes as indicated.

Article Snippet: Plasma obtained from animals after an overnight fast was used to quantify plasma cholesterol and triglyceride levels using Infinity colorimetric assay kits (TR22421 and TR13421, Thermo Fisher Scientific).

Techniques: Gene Expression, Western Blot, Reverse Transcription Polymerase Chain Reaction, Expressing, Control

Journal: The Journal of Biological Chemistry

Article Title: Cell type-specific control of cardiometabolic disease by the dileucine motif of the LDL receptor-related protein LRP1

doi: 10.1016/j.jbc.2026.111421

Figure Lengend Snippet: Plasma lipids and lipoproteins in Western diet-fed Lrp1 LL Ldlr −/− (LL) and Lrp1 AA Ldlr −/− mice. The LL and AA mice were fed a Western-type diet for 16 weeks. A , VLDL production was assessed in fasting animals (n = 3 per group) by measuring plasma triglyceride levels and determining changes in plasma triglyceride levels (Δtriglyceride) hourly after injection of Poloxamer 407 to inhibit lipolysis. B , plasma cholesterol and triglyceride levels were measured in 14 LL and 12 AA mice after an overnight fast. C , pooled plasma samples from fasting LL and AA mice were fractionated by FPLC for lipoprotein distribution analysis. The elution profiles were compared to elutions of standard chylomicron remnants/VLDL, IDL/LDL and HDL as indicated. D , plasma apolipoproteins were identified by Western blot analysis of plasma samples (n = 8 per group) for apoB (identifying both apoB100 and apoB48), apoE, and apoAI. Levels of apoB100, apoB48, and apoE were normalized to apoAI levels in plasma. All data were evaluated for significance by Student’s t test with p values as shown.

Article Snippet: Plasma obtained from animals after an overnight fast was used to quantify plasma cholesterol and triglyceride levels using Infinity colorimetric assay kits (TR22421 and TR13421, Thermo Fisher Scientific).

Techniques: Clinical Proteomics, Western Blot, Injection

Journal: The Journal of Biological Chemistry

Article Title: Cell type-specific control of cardiometabolic disease by the dileucine motif of the LDL receptor-related protein LRP1

doi: 10.1016/j.jbc.2026.111421

Figure Lengend Snippet: LRP1 with proximal dileucine motif mutation in bone marrow cells exacerbates atherosclerosis. Bone marrows from Lrp1 LL Ldlr −/− (LL) and Lrp1 AA Ldlr −/− (AA) mice were transplanted into Lrp1 LL Ldlr −/− recipient mice and then fed the Western type diet for 16 weeks ( A ) Plasma cholesterol levels in 8 LL and 6 AA mice, ( B ) plasma triglyceride levels in 8 LL and 6 AA mice, ( C ) atherosclerotic plaque area in the whole aorta of 7 mice per group, and ( D ) atherosclerotic lesion area in the aortic roots of 7 mice per group were analyzed. Bone marrows from LL mice were also transplanted into LL and AA recipient mice. After feeding the Western diet for 16 weeks, fasting plasma samples from 10 LL and 10 AA mice were analyzed for ( E ) cholesterol and ( F ) triglyceride levels. G , atherosclerotic lesion area in the whole aortas of LL and AA mice (n = 76 per group) and ( H ) in the aortic roots (n = 10 per group) were characterized. All data were evaluated for significance by Student’s t test with p values as shown.

Article Snippet: Plasma obtained from animals after an overnight fast was used to quantify plasma cholesterol and triglyceride levels using Infinity colorimetric assay kits (TR22421 and TR13421, Thermo Fisher Scientific).

Techniques: Mutagenesis, Western Blot, Clinical Proteomics

Journal: The Journal of Biological Chemistry

Article Title: Cell type-specific control of cardiometabolic disease by the dileucine motif of the LDL receptor-related protein LRP1

doi: 10.1016/j.jbc.2026.111421

Figure Lengend Snippet: LRP1 proximal dileucine mutation reduces mitochondrial respiration in cholesterol-loaded macrophages. Bone marrow-derived macrophages were incubated with or without acLDL prior to determination of oxygen consumption rates (OCR) ( A and B ). Oligomycin, FCCP, and rotenone/antimycin (rot/AA) were added to measure OCR and determination of basal ( C ) and maximal respiration ( D ). Etomoxir was added at 3 μM to inhibit fatty acid oxidation to determine OCR for assessment of basal respiration ( E ) and maximal respiration ( F ) due to non-fatty acid sources. Total mitochondrial ATP production ( G ) and etomoxir-resistant ATP production ( H ) were calculated from the OCR data. Differences between LL and AA samples under various treatment conditions were analyzed for significance by Student’s t test. ∗ indicates p < 0.05; ∗∗ indicates p < 0.01; ∗∗∗ p < 0.001; n.s. indicates not significant.

Article Snippet: Plasma obtained from animals after an overnight fast was used to quantify plasma cholesterol and triglyceride levels using Infinity colorimetric assay kits (TR22421 and TR13421, Thermo Fisher Scientific).

Techniques: Mutagenesis, Derivative Assay, Incubation

Journal: The Journal of Biological Chemistry

Article Title: Cell type-specific control of cardiometabolic disease by the dileucine motif of the LDL receptor-related protein LRP1

doi: 10.1016/j.jbc.2026.111421

Figure Lengend Snippet: LRP1 proximal dileucine mutation increased levels of mitochondrial fission proteins in cholesterol-loaded macrophages. Bone marrow macrophages isolated from Lrp1 LL Ldlr −/− (LL) and Lrp1 AA Ldlr −/− (AA) mice (n = 2 per group) were treated with acLDL for 24 h for cholesterol loading. Protein lysates were prepared for Western blot analysis of mitochondrial fission proteins: ( A ) mitochondrial fission factor MFF and ( B ) dynamin-related protein-1 DRP1; as well as mitochondrial fusion proteins: ( C ) mitofusin-2 (MFN2) and ( D ) optic atrophy-1 (OPA1). β-actin level in each sample was used as loading control. The data were normalized to the mean levels of expression in LL samples, with fold changes as indicated.

Article Snippet: Plasma obtained from animals after an overnight fast was used to quantify plasma cholesterol and triglyceride levels using Infinity colorimetric assay kits (TR22421 and TR13421, Thermo Fisher Scientific).

Techniques: Mutagenesis, Isolation, Western Blot, Control, Expressing

Journal: The Journal of Biological Chemistry

Article Title: Cell type-specific control of cardiometabolic disease by the dileucine motif of the LDL receptor-related protein LRP1

doi: 10.1016/j.jbc.2026.111421

Figure Lengend Snippet: LRP1 proximal dileucine motif mutation does not impact aggLDL uptake by reduced LRP1 association with mitochondria in cholesterol-loaded macrophages. A , bone marrow macrophages isolated from Lrp1 LL Ldlr −/− (LL) and Lrp1 AA Ldlr −/− mice (n = 6 per group) were incubated with DiI-labeled aggLDL overnight. Intracellular DiI accumulation was determined by fluorometry to determine cellular uptake of aggLDL. B , the bone marrow macrophages were treated with acLDL for 24 h for cholesterol loading. Total cell lysates and mitochondria fractions were prepared for Western blot analysis of total LRP1 levels and LRP1 association with mitochondria. β-actin levels in cell lysates and ATP5A levels in mitochondrial fractions were used as loading control. The data were normalized to the mean levels of expression in LL samples, with fold changes as indicated.

Article Snippet: Plasma obtained from animals after an overnight fast was used to quantify plasma cholesterol and triglyceride levels using Infinity colorimetric assay kits (TR22421 and TR13421, Thermo Fisher Scientific).

Techniques: Mutagenesis, Isolation, Incubation, Labeling, Western Blot, Control, Expressing