Dataset Information

Apolipoprotein A-IV: A Multifunctional Protein Involved in Protection against Atherosclerosis and Diabetes.

ABSTRACT: Apolipoprotein A-IV (apoA-IV) is a lipid-binding protein, which is primarily synthesized in the small intestine, packaged into chylomicrons, and secreted into intestinal lymph during fat absorption. In the circulation, apoA-IV is present on chylomicron remnants, high-density lipoproteins, and also in lipid-free form. ApoA-IV is involved in a myriad of physiological processes such as lipid absorption and metabolism, anti-atherosclerosis, platelet aggregation and thrombosis, glucose homeostasis, and food intake. ApoA-IV deficiency is associated with atherosclerosis and diabetes, which renders it as a potential therapeutic target for treatment of these diseases. While much has been learned about the physiological functions of apoA-IV using rodent models, the action of apoA-IV at the cellular and molecular levels is less understood, let alone apoA-IV-interacting partners. In this review, we will summarize the findings on the molecular function of apoA-IV and apoA-IV-interacting proteins. The information will shed light on the discovery of apoA-IV receptors and the understanding of the molecular mechanism underlying its mode of action.

SUBMITTER: Qu J

PROVIDER: S-EPMC6523623 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Apolipoprotein A-IV: A Multifunctional Protein Involved in Protection against Atherosclerosis and Diabetes.

Qu Jie J Ko Chih-Wei CW Tso Patrick P Bhargava Aditi A

Cells 20190405 4

Apolipoprotein A-IV (apoA-IV) is a lipid-binding protein, which is primarily synthesized in the small intestine, packaged into chylomicrons, and secreted into intestinal lymph during fat absorption. In the circulation, apoA-IV is present on chylomicron remnants, high-density lipoproteins, and also in lipid-free form. ApoA-IV is involved in a myriad of physiological processes such as lipid absorption and metabolism, anti-atherosclerosis, platelet aggregation and thrombosis, glucose homeostasis, a ...[more]

PMID: 30959835

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Project description:Chemokines are important in macrophage recruitment and the progression of atherosclerosis. The 'M3' chemokine binding protein inactivates key chemokines involved in atherosclerosis (e.g. CCL2, CCL5 and CX3CL1). We aimed to determine the effect of M3 on plaque development and composition. In vitro chemotaxis studies confirmed that M3 protein inhibited the activity of chemokines CCL2, CCL5 and CX3CL1 as primary human monocyte migration as well as CCR2-, CCR5- and CX3CR1-directed migration was attenuated by M3. In vivo, adenoviruses encoding M3 (AdM3) or green fluorescence protein (AdGFP; control) were infused systemically into apolipoprotein (apo)-E-/- mice. Two models of atherosclerosis development were used in which the rate of plaque progression was varied by diet including: (1) a 'rapid promotion' model (6-week high-fat-fed) and (2) a 'slow progression' model (12-week chow-fed). Plasma chemokine activity was suppressed in AdM3-infused mice as indicated by significantly less monocyte migration towards AdM3 mouse plasma ex vivo (29.56%, p = 0.014). In the 'slow progression' model AdM3 mice had reduced lesion area (45.3%, p = 0.035) and increased aortic smooth muscle cell α-actin expression (60.3%, p = 0.014). The reduction in lesion size could not be explained by changes in circulating inflammatory monocytes as they were higher in the AdM3 group. In the 'rapid promotion' model AdM3 mice had no changes in plaque size but reduced plaque macrophage content (46.8%, p = 0.006) and suppressed lipid deposition in thoracic aortas (66.9%, p<0.05). There was also a reduction in phosphorylated p65, the active subunit of NF-κb, in the aortas of AdM3 mice (37.3%, p<0.0001). M3 inhibited liver CCL2 concentrations in both models with no change in CCL5 or systemic chemokine levels. These findings show M3 causes varying effects on atherosclerosis progression and plaque composition depending on the rate of lesion progression. Overall, our studies support a promising role for chemokine inhibition with M3 for the treatment of atherosclerosis.

Dataset Information

Apolipoprotein A-IV: A Multifunctional Protein Involved in Protection against Atherosclerosis and Diabetes.

Publications

Apolipoprotein A-IV: A Multifunctional Protein Involved in Protection against Atherosclerosis and Diabetes.

Similar Datasets

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