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Cited by 111Atherosclerosis and Cardiovascular DiseasesS100 Proteins and AnnexinsDermatological and Skeletal Disorders

S100A12 in Vascular Smooth Muscle Accelerates Vascular Calcification in Apolipoprotein E–Null Mice by Activating an Osteogenic Gene Regulatory Program

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Hofmann Bowman, Marion A., Gawdzik, Joseph, Bukhari, Usama, Husain, Aliya N., Toth, Peter T., Kim, Gene, Earley, Judy, McNally, Elizabeth M.·2011·Arteriosclerosis, Thrombosis, and Vascular Biology
DOI 10.1161/atvbaha.110.217745PMC PMC3364048
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Abstract

Objective—: The proinflammatory cytokine S100A12 is associated with coronary atherosclerotic plaque rupture. We previously generated transgenic mice with vascular smooth muscle–targeted expression of human S100A12 and found that these mice developed aortic aneurysmal dilation of the thoracic aorta. In the current study, we tested the hypothesis that S100A12 expressed in vascular smooth muscle in atherosclerosis-prone apolipoprotein E (ApoE)–null mice would accelerate atherosclerosis. Methods and Results—: ApoE-null mice with or without the S100A12 transgene were analyzed. We found a 1.4-fold increase in atherosclerotic plaque size and more specifically a large increase in calcified plaque area (45% versus 7% of innominate artery plaques and 18% versus 10% of aortic root plaques) in S100A12/ApoE-null mice compared with wild-type/ApoE-null littermates. Expression of bone morphogenic protein and other osteoblastic genes was increased in aorta and cultured vascular smooth muscle, and importantly, these changes in gene expression preceded the development of vascular calcification in S100A12/ApoE-null mice. Accelerated atherosclerosis and vascular calcification were mediated, at least in part, by oxidative stress because inhibition of NADPH oxidase attenuated S100A12-mediated osteogenesis in cultured vascular smooth muscle cells. S100A12 transgenic mice in the wild-type background (ApoE+/+) showed minimal vascular calcification, suggesting that S100A12 requires a proinflammatory/proatherosclerotic environment to induce osteoblastic differentiation and vascular calcification. Conclusion—: Vascular smooth muscle S100A12 accelerates atherosclerosis and augments atherosclerosis-triggered osteogenesis, reminiscent of features associated with plaque instability.

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  • Specific genetic modulation of VSMC osteochondrogenesis in vivo leads to altered calcification in models of atherosclerosis.

    “Furthermore, specific genetic modulation of VSMC osteochondrogenesis in vivo leads to altered calcification in models of atherosclerosis 160-162 .”

    From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [161]

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Authors
Hofmann Bowman, M. A., Gawdzik, J., Bukhari, U., Husain, A. N., Toth, P. T., Kim, G., Earley, J., & McNally, E. M.
Affiliations
  • From the Department of Medicine, Section of Cardiology (M.A.H.B., J.G., U.B., P.T.T., G.K., J.E., E.M.M.) and Department of Pathology (A.N.H.), University of Chicago, Chicago, Ill.
  • University of Chicago (US)
ORCID
Venue
Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2011-02
Volume
31
Issue
2
Pages
337-344
ISSN
  • 1079-5642 (ISSN-L)
  • 1524-4636
DOI
10.1161/atvbaha.110.217745
PMC
PMC3364048
OpenAlex
W2140905655
Cited by
111
References
37
Citations by year
2026: 1 · 2025: 4 · 2024: 6 · 2023: 3 · 2022: 8 · 2021: 7 · 2020: 5 · 2019: 5 · 2018: 7 · 2017: 8 · 2016: 7 · 2015: 5 · 2014: 13 · 2013: 13 · 2012: 7
FWCI
4.40
Type
journal article
Language
en
Open access
Locations
  • Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5r01hl078926-05, 1k08hl090917-01a1)
  • National Heart, Lung, and Blood Institute (5R01HL078926-05, R01-HL-078926, K08-HL090917, K08HL098565, K08 HL090917-02)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Dermatological and Skeletal Disorders
Keywords
S100A12, vascular smooth muscle, vascular calcification, atherosclerosis, apolipoprotein E-null mice, osteogenic differentiation, bone morphogenic proteins, NADPH oxidase, oxidative stress, plaque vulnerability, aortic aneurysm
MeSH terms
S100A12 Protein, Animals, Apolipoproteins E, Calcinosis, Cells, Cultured, Disease Models, Animal, Gene Expression Regulation, Humans, Mice, Inbred C57BL, Mice, Transgenic, Muscle, Smooth, Vascular, S100 Proteins, Osteogenesis, Signal Transduction, Mice, Knockout, Oxidative Stress, NADPH Oxidases, Mice

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