Department of Life Science, College of Natural Sciences, Hanyang Institute of Bioscience and Biotechnology, Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea.
Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea.
Department of Biomedicine and Health Sciences, Graduate School, The Catholic University of Korea, Seoul, 06591, Republic of Korea.
Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea.
Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, 28116, Republic of Korea.
Cardiovascular Center and Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
Samsung Genome Institute, Samsung Medical Center, Seoul, 06351, Republic of Korea.
Department of Pharmacology and Regenerative Medicine, The University of Illinois College of Medicine, Chicago, IL, 60612, USA.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, 04763, Republic of Korea.
Division of Cardiovascular Surgery, Department of Thoracic and Cardiovascular Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
Integrative Research Center for Cerebrovascular and Cardiovascular Diseases, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
Division of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
Division of Cardiology, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, 11765, Republic of Korea.
Catholic Research Institute for Intractable Cardiovascular Disease (CRID), College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea.
Department of Thoracic and Cardiovascular Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, 11765, Republic of Korea.
Heart-Immune-Brain Network Research Center, Department of Life Science, Ewha Womans University, Seoul, 03760, Republic of Korea.
Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, 16419, Republic of Korea.
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences &Technology, Sungkyunkwan University, Seoul, 06355, Republic of Korea.
Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. haeocklee@catholic.ac.kr.
Department of Biomedicine and Health Sciences, Graduate School, The Catholic University of Korea, Seoul, 06591, Republic of Korea. haeocklee@catholic.ac.kr.
Department of Life Science, College of Natural Sciences, Hanyang Institute of Bioscience and Biotechnology, Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea. jchoi75@hanyang.ac.kr.
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-IIhi 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.
