| First Author | Lee SH | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 5461 |
| PubMed ID | 36115863 | Mgi Jnum | J:357326 |
| Mgi Id | MGI:7340794 | Doi | 10.1038/s41467-022-33202-2 |
| Citation | Lee SH, et al. (2022) Single-cell transcriptomics reveal cellular diversity of aortic valve and the immunomodulation by PPARgamma during hyperlipidemia. Nat Commun 13(1):5461 |
| abstractText | Valvular inflammation triggered by hyperlipidemia has been considered as an important initial process of aortic valve disease; however, cellular and molecular evidence remains unclear. Here, we assess the relationship between plasma lipids and valvular inflammation, and identify association of low-density lipoprotein with increased valvular lipid and macrophage accumulation. Single-cell RNA sequencing analysis reveals the cellular heterogeneity of leukocytes, valvular interstitial cells, and valvular endothelial cells, and their phenotypic changes during hyperlipidemia leading to recruitment of monocyte-derived MHC-II(hi) macrophages. Interestingly, we find activated PPARgamma pathway in Cd36(+) valvular endothelial cells increased in hyperlipidemic mice, and the conservation of PPARgamma activation in non-calcified human aortic valves. While the PPARgamma inhibition promotes inflammation, PPARgamma activation using pioglitazone reduces valvular inflammation in hyperlipidemic mice. These results show that low-density lipoprotein is the main lipoprotein accumulated in the aortic valve during hyperlipidemia, leading to early-stage aortic valve disease, and PPARgamma activation protects the aortic valve against inflammation. |
