Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:


Written in Published in Earliest date Latest date

Sorted by

Results per page:

You searched for +publisher:"Temple University" +contributor:("Zhou, Zhaolan;"). One record found.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters

Temple University

1. Jan, Michael. Novel Mechanisms Underlying Homocysteine-Suppressed Endothelial Cell Growth.

Degree: PhD, 2014, Temple University


Cardiovascular disease (CVD) is the leading cause of death worldwide, and is projected to remain so for at least the next decade. Ever since its discovery in the urine and blood of children with inborn errors of metabolism, homocysteine (Hcy) at elevated plasma concentrations has been associated with CVD clinically and epidemiologically. Observational studies and meta-analyses have noted that changes in plasma Hcy by 5μM increase the odds ratio of developing coronary artery disease by 1.6-1.8 among other CVD. Clinical trials aimed at reducing plasma Hcy for benefit against development of subsequent cardiovascular events have had unconvincing results, but have moreover failed to address the mechanisms by which Hcy contributes to CVD. Recommendations from national agencies like the American Heart Association and the United States Preventive Services Task Force emphasize primordial prevention as a way to combat CVD. Reducing plasma Hcy as secondary and primary interventions does not fulfill this recommendation. In order to best understand the role of Hcy in CVD, an investigation into its mechanisms of action must be undertaken before measures of primordial prevention can be devised. Numerous experimental studies in the literature identify vascular endothelium as a target for the pathological effects of Hcy. Endothelial injury and impairment are contributory processes to atherosclerosis, and Hcy has been demonstrated to inhibit endothelial cell (EC) growth and proliferation through mechanisms involving cell cycle arrest, oxidative stress, and programmed cell death in vitro. Animal models have also confirmed that high levels of Hcy accelerate atherosclerotic plaque development and lead to impairment of vascular reendothelialization following injury. Hcy has been shown to have the opposite effect in vascular smooth muscle cells (SMC), causing their proliferation and again contributing to atherosclerosis. The cell-type specificity of Hcy remains to be understood, and among the aims of this research was to further characterize the effects of Hcy in EC. The overarching goal was discovery in order to direct future investigations of Hcy-mediated pathology. To begin, the first investigation considered the transcriptional and regulatory milieu in EC following exposure to Hcy. High-throughput screening using microarrays determined the effect of Hcy on 26,890 mRNA and 1,801 miRNA. Two different in vitro models of hyperhomocysteinemia (HHcy) were considered in this analysis. The first used a high dose of 500µ Hcy to mimic plasma concentrations of patients wherein the transsulfuration pathway of Hcy metabolism is impaired as in inborn cystathionine-ß-synthase deficiency. The other set of conditions used 50µ Hcy in the presence of adenosine to approximate impairment of the remethylation pathway of Hcy metabolism wherein s-adenosylhomocysteine accumulates, thus inhibiting s-adenosylmethionine formation and methylation reactions. These distinctions are important because most clinical trials do not distinguish between…

Advisors/Committee Members: Wang, Hong;, Ashby, Barrie, Autieri, Michael V., Merali, Salim, Yang, Xiao-Feng, Zhou, Zhaolan;.

Subjects/Keywords: Pharmacology;

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Jan, M. (2014). Novel Mechanisms Underlying Homocysteine-Suppressed Endothelial Cell Growth. (Doctoral Dissertation). Temple University. Retrieved from,264103

Chicago Manual of Style (16th Edition):

Jan, Michael. “Novel Mechanisms Underlying Homocysteine-Suppressed Endothelial Cell Growth.” 2014. Doctoral Dissertation, Temple University. Accessed April 15, 2021.,264103.

MLA Handbook (7th Edition):

Jan, Michael. “Novel Mechanisms Underlying Homocysteine-Suppressed Endothelial Cell Growth.” 2014. Web. 15 Apr 2021.


Jan M. Novel Mechanisms Underlying Homocysteine-Suppressed Endothelial Cell Growth. [Internet] [Doctoral dissertation]. Temple University; 2014. [cited 2021 Apr 15]. Available from:,264103.

Council of Science Editors:

Jan M. Novel Mechanisms Underlying Homocysteine-Suppressed Endothelial Cell Growth. [Doctoral Dissertation]. Temple University; 2014. Available from:,264103