Abstract Body: Introduction: Micronanoplastics (MNPs) are a ubiquitous environmental contaminant linked to cardiovascular disease in humans. Mechanisms by which MNPs affect atherosclerosis remain obscure. Animal models of atherosclerosis permit the study of MNP-atheroma interactions in a controlled setting. MNPs derived from natural ocean sources are a novel model, better mimicking human environmental exposure compared to commercial nanospheres. Prior data suggests diet type may influence the efficiency of MNP uptake.
Hypothesis: Dietary ocean-derived MNPs influence atherosclerosis development and solid organ MNP accumulation in a diet-dependent manner.
Methods: Adult ApoE^-/- mice (n=5-7/group) were fed Standard (SD) or Western diet (WD) ± 1% (w/w) ocean MNPs (<20 µm) milled into chow. After 6 or 12 weeks of exposure, animals underwent atherogenic measures including aortic pulse wave velocity (PWV), aortic Oil Red O (ORO), aortic root histologic analysis, and pin myography (5 mm aortic rings) for wall stiffness. Bulk RNAseq of aortic tissue was performed. Brain, liver and kidney underwent pyrolysis-gas chromatography/mass spectroscopy (Py-GC/MS) to measure the concentration of MNPs by polymer.
Results: At 6 weeks, PWV shows greater vessel stiffness in WD+MNP (307 cm/s) compared WD only (263 cm/s, P=0.01) animals. At 12 weeks, vessel stiffening was greater in SD+MNP compared to SD (271 vs 247.8, P=0.016). ORO disclosed 3-fold greater aortic atheroma area in MNP-fed animals eating WD (0.66 mm²) versus non-MNP (0.19 mm², P<0.01). Aortic root atherosclerotic area was 2.8-fold greater in MNP-fed animals (16.4 mm²) versus control (5.8 mm², P<0.01). Myography confirmed greater elastin modulus in MNP-fed animals (660 vs 587 AU, P<0.05)) at 6 weeks. Bulk RNAseq shows upregulation of pro-atherogenic genes commonly expressed in vascular smooth muscle cells and macrophages including Slc2a5 (10.6 fold), Acly (3.6 fold), and Lep (2 fold) (all P<0.01). At 6 weeks, liver MNP concentrations in the WD+MNP animals were greater than control (132.8 vs 335.5 µg/g tissue, P=0.02). At 12 weeks, SD+MNP mice had higher levels of plastics in the brain (1503 vs 612 ug/g tissue, P=0.016), and the WD+MNP-fed mice had higher levels in the liver (609.0 vs 112.8 µg/g tissue, P<0.01).
Conclusions: Exposure time and diet type have strong effects on aortic atherogenesis and nanoplastics accumulation in solid organs. Additional study regarding mechanisms of MNP impacts on atherosclerosis is warranted.