Short‐term LPS induces Aortic Valve thickening in ApoE*3Leiden mice

Short‐term LPS induces Aortic Valve thickening in ApoE*3Leiden mice

van Broekhoven, A.
Krijnen, P.A.J.
Fuijkschot, W.W.
Morrison, M.C.
Zethof, I.P.A.
van Wieringen, W.N.
Smulders, Y.M.
Niessen, H.W.M.
Vonk, A.B.A.

2019

Background Recently, it was shown that 12 weeks of lipopolysacharide (LPS) administration to non‐atherosclerotic mice induced thickening of the aortic heart valve (AV). Whether such effects may also occur even earlier is unknown. As most patients with AV stenosis also have atherosclerosis, we studied the short‐term effect of LPS on the AVs in an atherosclerotic mouse model. Methods ApoE*3Leiden mice, on an atherogenic diet, were injected intra‐peritoneally with either LPS or phosphate buffered saline (PBS), and sacrificed 2 or 15 days later. AVs were assessed for size, fibrosis, glycosaminoglycans (GAGs), lipids, calcium deposits, iron deposits and inflammatory cells. Results LPS‐injection caused an increase in maximal leaflet thickness at 2 days (128.4 μm) compared to PBS‐injected mice (67.8 μm; p=0.007), whereas at 15 days this was not significantly different. LPS‐injection did not significantly affect average AV thickness on day 2 (37.8 μm), but did significantly increase average AV thickness at day 15 (41.6 μm; p=0.038) compared to PBS‐injected mice (31.7 μm and 32.3 μm respectively). LPS‐injection did not affect AV fibrosis, GAGs and lipid content. Furthermore, no calcium deposits were found. Iron deposits, indicative for valve hemorrhage, were observed in one AV of the PBS‐injected group (a day 2 mouse; 9.1%) and in five AVs of the LPS‐injected group (both day 2‐ and 15 mice; 29.4%). No significant differences in inflammatory cell infiltration were observed upon LPS‐injection. Conclusion Short‐term LPS apparently has the potential to increase AV thickening and hemorrhage. These results suggest that systemic inflammation can acutely compromise AV structure.

Aortic vlve stenosis
Atherosclerosis
Systematic inflammation
Lipopolysaccharide

http://resolver.tudelft.nl/uuid:ed64bf10-0199-499c-9039-37d8d00156ea

https://doi.org/10.1111/eci.13121

866978

European Journal of Clinical Investigation, 49 (7), e13121

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