Doctor of Philosophy (PhD)
First Advisor's Name
First Advisor's Committee Title
Second Advisor's Name
Second Advisor's Committee Title
Third Advisor's Name
Third Advisor's Committee Title
Fourth Advisor's Name
Fourth Advisor's Committee Title
Environmental Health Sciences, Vascular Disease, Molecular Biology, Gene-Environment Interactions
Date of Defense
Tumor-like proliferative vascular lesions manifest in several diseases such as peripheral arterial disease (PAD) and atherosclerosis (AS) after arterial injury. The cause of the vascular cell dysfunction in PAD patients is not known. Our recent novel discovery shows that inhibitor of differentiation 3 (ID3) is highly expressed in intimal lesions of clinical vascular disease samples. The central hypothesis of our study is: estrogenic chemical induced dysregulation of ID3 target genes is involved in the development of vascular disease. NHANES data analysis demonstrated higher geometric levels of all 6 PCB congeners in both PAD diagnosed participants and participants at risk of AS when compared to the rest of the population. Adjusted models showed association between higher exposure of PCBs, phthalates, BPA, and increased risk of PAD. Furthermore PCB153 was shown to have the highest geometric mean amongst all PCB congeners in both participants diagnosed with PAD and at risk of AS. Gene expression of ID3 & ID3 candidate targets in blood & tissue studies identified ID3 & ID3 candidate target genes as a driver of vascular disease. Overlapping ID3 & ID3 candidate target genes included: ABCB6, ACP1, BYSL, CAD, CDH15, DCBLD2, DHRS3, DNMT1, ID3, MCM4, and NDUFA7. The ID3 target genes involved in the: focal adhesion pathway were ACTN1, COL1A2, COL3A1, COL6A1, CTNNB1, IBSP, ID3, ITGA8, and MYL2; ECM-receptor interaction were COL1A2, COL3A1, COL6A1, IBSP, ID3, and ITGA8; oxidative phosphorylation pathway ATP5D, ATP5H, ATP6V0B, ATP6V0D1, ATP6V1B2, COX5A, COX7C, COX8A, CYC1, ID3, NDUFA1, NDUFA7, NDUFS4, NDUFV1, NDUFV2; and cell cycle pathway ANAPC10, ATM, CDKN2B, E2F5, MCM3, and MCM4. In summary our results showed an association between exposure to PCBs, phthalates, BPA, and increased risk of PAD and AS, and possible molecular mechanisms of interaction of ID3 target genes and estrogenic chemicals involved in PAD and AS.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 License.
Avecilla, Vincent E., "ID3, Estrogenic Chemicals, and the Pathogenesis of Tumor-Like Proliferative Vascular Lesions" (2017). FIU Electronic Theses and Dissertations. 3519.
Available for download on Sunday, December 08, 2019
In Copyright - Non-Commmercial Use Permitted. URI: http://rightsstatements.org/vocab/InC-NC/1.0/
This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. In addition, no permission is required from the rights-holder(s) for non-commercial uses. For other uses you need to obtain permission from the rights-holder(s).