Changing topographic Hox expression in blood vessels results in regionally distinct vessel wall remodeling
Open accessAbstract
Summary: The distinct topographic Hox expression patterns observed in vascular smooth muscle cells (VSMCs) of the adult cardiovascular system suggest that these transcriptional regulators are critical for maintaining region-specific physiological properties of blood vessels. To test this proposition, we expanded the vascular Hoxc11 expression domain normally restricted to the lower limbs by utilizing an innovative integrated tetracycline regulatory system and Transgelin promoter elements to induce Hoxc11 expression universally in VSMCs of transgenic mice. Ectopic Hoxc11 expression in carotid arteries, aortic arch and descending aorta resulted in drastic vessel wall remodeling involving elastic laminae fragmentation, medial smooth muscle cell loss, and intimal lesion formation. None of these alterations were observed upon induction of Hoxc11 transgene expression in the femoral artery, i.e. the natural Hoxc11 activity domain, although this vessel was greatly enlarged, comparable to the topographically restricted vascular changes seen in Hoxc11−/− mice. To begin defining Hoxc11-controlled pathways of vascular remodeling, we performed immunolabeling studies in conjunction with co-transfection and chromatin immunoprecipitation (ChIP) assays using mouse vascular smooth muscle (MOVAS) cells. The results suggest direct transcriptional control of two members of the matrix metalloproteinase (Mmp) family, including Mmp2 and Mmp9 that are known as key players in the inception and progression of vascular remodeling events. In summary, the severe vascular abnormalities resulting from the induced dysregulated expression of a Hox gene with regional vascular patterning functions suggest that proper Hox function and regulation is critical for maintaining vascular functional integrity.
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There is evidence for positional identity among VSMCs along the anterior-posterior, dorso-ventral, and right-left axes of the embryo.
“Furthermore, there is evidence for positional identity among VSMCs along the anterior-posterior, dorso-ventral, and right-left axes of the embryo 28-30 .”
From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [30]
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- Authors
- Pruett, N. D., Hajdu, Z., Zhang, J., Visconti, R. P., Kern, M. J., Wellik, D. M., Majesky, M. W., & Awgulewitsch, A.
- Affiliations
- Department of Medicine
- Medical University of South Carolina (US)
- University of Michigan (US)
- University of Washington (US)
- Corresponding author
- Awgulewitsch, Alexander
- Venue
- Biology Open
- Publisher
- The Company of Biologists
- Published
- 2012-03-20
- Volume
- 1
- Issue
- 5
- Pages
- 430-435
- ISSN
- 2046-6390 (ISSN-L)
- PMC
- PMC3507213
- OpenAlex
- W2127504174
- Cited by
- 26
- References
- 36
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 4 · 2016: 1 · 2015: 3 · 2014: 2 · 2013: 3
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biology Open (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Heart, Lung, and Blood Institute (R01HL093594)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR047204)
- National Center for Research Resources (P20RR016434)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- HOXC11, vascular smooth muscle cells, vascular remodeling, ectopic expression, matrix metalloproteinases, MMP-2, MMP-9, intimal lesions, carotid artery, aorta, femoral artery, transcriptional regulation
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