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2017

Theses and Dissertations--Pharmacology and Nutritional Sciences

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Telomerase Reverse Transcriptase In Atherosclerosis, Hua Qing Jan 2017

Telomerase Reverse Transcriptase In Atherosclerosis, Hua Qing

Theses and Dissertations--Pharmacology and Nutritional Sciences

Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase and the limiting factor for the enzyme activity. The expression of TERT and telomerase activity is increased in atherosclerotic plaques. However, the role of TERT dysregulation during atherosclerosis formation remains unknown.

The work herein first identified a multi-tiered regulation of TERT expression in smooth muscle cells (SMC) through histone deacetylase (HDAC) inhibition. HDAC inhibition induces TERT transcription and promoter activation. At the protein level in contrast, HDAC inhibition decreases TERT protein abundance through enhanced degradation, which decreases telomerase activity and induces senescence. Furthermore, during vascular remodeling in vivo, TERT protein …