Atherosclerosis in Different Vascular Locations Unbiasedly Approached with Mouse Genetics
Atherosclerosis in different vascular locations leads to distinct clinical consequences, such as ischemic stroke and myocardial infarction. Genome-wide association studies in humans revealed that genetic loci responsible for carotid plaque and coronary artery disease were not overlapping, suggesting...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/11/12/1427 |
| _version_ | 1797546429932109824 |
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| author | Yukako Kayashima Nobuyo Maeda-Smithies |
| author_facet | Yukako Kayashima Nobuyo Maeda-Smithies |
| author_sort | Yukako Kayashima |
| collection | DOAJ |
| description | Atherosclerosis in different vascular locations leads to distinct clinical consequences, such as ischemic stroke and myocardial infarction. Genome-wide association studies in humans revealed that genetic loci responsible for carotid plaque and coronary artery disease were not overlapping, suggesting that distinct genetic pathways might be involved for each location. While elevated plasma cholesterol is a common risk factor, plaque development in different vascular beds is influenced by hemodynamics and intrinsic vascular integrity. Despite the limitation of species differences, mouse models provide platforms for unbiased genetic approaches. Mouse strain differences also indicate that susceptibility to atherosclerosis varies, depending on vascular locations, and that the location specificity is genetically controlled. Quantitative trait loci analyses in mice suggested candidate genes, including <i>Mertk</i> and <i>Stab2</i>, although how each gene affects the location-specific atherosclerosis needs further elucidation. Another unbiased approach of single-cell transcriptome analyses revealed the presence of a small subpopulation of vascular smooth muscle cells (VSMCs), which are “hyper-responsive” to inflammatory stimuli. These cells are likely the previously-reported Sca1<sup>+</sup> progenitor cells, which can differentiate into multiple lineages in plaques. Further spatiotemporal analyses of the progenitor cells are necessary, since their distribution pattern might be associated with the location-dependent plaque development. |
| first_indexed | 2024-03-10T14:29:38Z |
| format | Article |
| id | doaj.art-ef2ac59af09443a790753bc9cd1d5137 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T14:29:38Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-ef2ac59af09443a790753bc9cd1d51372023-11-20T22:42:02ZengMDPI AGGenes2073-44252020-11-011112142710.3390/genes11121427Atherosclerosis in Different Vascular Locations Unbiasedly Approached with Mouse GeneticsYukako Kayashima0Nobuyo Maeda-Smithies1Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, CB#7525, 701 Brinkhous-Bullitt Building, Chapel Hill, NC 27599-7525, USADepartment of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, CB#7525, 701 Brinkhous-Bullitt Building, Chapel Hill, NC 27599-7525, USAAtherosclerosis in different vascular locations leads to distinct clinical consequences, such as ischemic stroke and myocardial infarction. Genome-wide association studies in humans revealed that genetic loci responsible for carotid plaque and coronary artery disease were not overlapping, suggesting that distinct genetic pathways might be involved for each location. While elevated plasma cholesterol is a common risk factor, plaque development in different vascular beds is influenced by hemodynamics and intrinsic vascular integrity. Despite the limitation of species differences, mouse models provide platforms for unbiased genetic approaches. Mouse strain differences also indicate that susceptibility to atherosclerosis varies, depending on vascular locations, and that the location specificity is genetically controlled. Quantitative trait loci analyses in mice suggested candidate genes, including <i>Mertk</i> and <i>Stab2</i>, although how each gene affects the location-specific atherosclerosis needs further elucidation. Another unbiased approach of single-cell transcriptome analyses revealed the presence of a small subpopulation of vascular smooth muscle cells (VSMCs), which are “hyper-responsive” to inflammatory stimuli. These cells are likely the previously-reported Sca1<sup>+</sup> progenitor cells, which can differentiate into multiple lineages in plaques. Further spatiotemporal analyses of the progenitor cells are necessary, since their distribution pattern might be associated with the location-dependent plaque development.https://www.mdpi.com/2073-4425/11/12/1427atherosclerosisapolipoprotein E-deficient mouseassociation studyquantitative trait locusvascular geometryendothelial cell |
| spellingShingle | Yukako Kayashima Nobuyo Maeda-Smithies Atherosclerosis in Different Vascular Locations Unbiasedly Approached with Mouse Genetics Genes atherosclerosis apolipoprotein E-deficient mouse association study quantitative trait locus vascular geometry endothelial cell |
| title | Atherosclerosis in Different Vascular Locations Unbiasedly Approached with Mouse Genetics |
| title_full | Atherosclerosis in Different Vascular Locations Unbiasedly Approached with Mouse Genetics |
| title_fullStr | Atherosclerosis in Different Vascular Locations Unbiasedly Approached with Mouse Genetics |
| title_full_unstemmed | Atherosclerosis in Different Vascular Locations Unbiasedly Approached with Mouse Genetics |
| title_short | Atherosclerosis in Different Vascular Locations Unbiasedly Approached with Mouse Genetics |
| title_sort | atherosclerosis in different vascular locations unbiasedly approached with mouse genetics |
| topic | atherosclerosis apolipoprotein E-deficient mouse association study quantitative trait locus vascular geometry endothelial cell |
| url | https://www.mdpi.com/2073-4425/11/12/1427 |
| work_keys_str_mv | AT yukakokayashima atherosclerosisindifferentvascularlocationsunbiasedlyapproachedwithmousegenetics AT nobuyomaedasmithies atherosclerosisindifferentvascularlocationsunbiasedlyapproachedwithmousegenetics |