Single-cell transcriptomics reveal cellular diversity of aortic valve and the immunomodulation by PPARγ during hyperlipidemia.
Seung Hyun LeeNayoung KimMinkyu KimSang-Ho WooInhee HanJisu ParkKyeongdae KimKyu Seong ParkKibyeong KimDahee ShimSang-Eun ParkJing Yu ZhangDu-Min GoDae-Yong KimWon Kee YoonSeung-Pyo LeeJongsuk ChungKi-Wook KimJung Hwan ParkSeung Hyun LeeSak LeeSoo-Jin AnnSang-Hak LeeHyo-Suk AhnSeong Cheol JeongTae Kyeong KimGoo Taeg OhWoong-Yang ParkHae-Ock LeeJae-Hoon ChoiPublished in: Nature communications (2022)
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 PPARγ pathway in Cd36 + valvular endothelial cells increased in hyperlipidemic mice, and the conservation of PPARγ activation in non-calcified human aortic valves. While the PPARγ inhibition promotes inflammation, PPARγ 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 PPARγ activation protects the aortic valve against inflammation.
Keyphrases
- aortic valve
- single cell
- endothelial cells
- low density lipoprotein
- transcatheter aortic valve replacement
- transcatheter aortic valve implantation
- aortic valve replacement
- oxidative stress
- aortic stenosis
- insulin resistance
- rna seq
- high fat diet induced
- high fat diet
- early stage
- fatty acid
- atrial fibrillation
- induced apoptosis
- adipose tissue
- vascular endothelial growth factor
- high glucose
- dna methylation
- metabolic syndrome
- lymph node
- peripheral blood
- type diabetes
- cell proliferation
- heart failure
- signaling pathway
- radiation therapy
- gene expression
- pulmonary hypertension
- coronary artery disease
- left ventricular
- oral anticoagulants