Leili Behrooz, MD
Postdoctoral Fellow
Boston University Chobanian & Avedisian School of Medicine
Vascular Biology

Type 2 diabetes mellitus is a key public health problem worldwide with current trends predicting that 500 million people will have diabetes in 2035. The escalating prevalence of type 2 diabetes worldwide presents a critical cardiovascular challenge. Patients with type 2 diabetes experience accelerated vascular aging, premature atherosclerotic cardiovascular disease, and increased rates of cardiovascular events. There is considerable interest in the clinical cardiovascular benefits of new agents to treat type 2 diabetes including sodium-glucose cotransporter-2 (SGLT2) inhibitors such as dapagliflozin. However, the mechanisms of cardiovascular activity remains incompletely understood. Metabolic disturbances underlie the systemic vascular dysfunction in type 2 diabetes. Elevated glucose and lipids alter signal transduction thereby changing gene expression resulting disturbing endothelial homeostasis. Alterations in endothelial function including inflammation and reduced nitric oxide production promote atherogenesis in diabetes.

Several studies suggest activity of SGLT2 inhibitors on vascular function in animal models and humans. The robust clinical trial evidence with these classes of diabetes medications has not yet been accompanied by complete mechanistic evidence in the vasculature.
Combining vascular functional assessment with targeted endothelial cell gene expression and nitric oxide characterization will expand critical evidence about the mechanisms of action. Prior clinical studies evaluating the effects of SGLT-2 inhibitors have been limited to evaluation of vascular health without measures of endothelial cell phenotype that will provide additional mechanistic information. Dapagliflozin, a SGLT2 inhibitor, has effects on endothelial cell inflammation in cultured cells and improved vasodilation in animal models; however the effect on endothelial cell health in patients is not well-defined. Emerging experimental evidence in preclinical models also links SGLT2 inhibitors to reduction in mitochondrial oxidative stress.
We aim to investigate treatment with a SGLT2 inhibitor for diabetes will alter endothelial cell phenotype and ncRNA or biomarkers. We plan to test this hypothesis by conducting an interventional crossover study with dapagliflozin. We anticipate that evaluating endothelial cell phenotype will provide key additional information regarding the ability of novel treatments for type 2 diabetes to restore vascular health. Our study will provide novel evidence about endothelial cell effects of dapagliflozin that link to both animal models of diabetes and clinical trial data.

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

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  1. Abumoawad A, Shatla I, Behrooz L, Eberhardt RT, Hamburg N, Sedhom R, Elgendy IY, Kumbhani DJ, Cameron SJ, Elbadawi A. Temporal Trends in the Utilization of Advanced Therapies Among Patients with Acute Pulmonary Embolism: Insights from a National Database. Eur Heart J Acute Cardiovasc Care. 2023 Aug 07.View Related Profiles. PMID: 37549064
  2. Behrooz L, Abumoawad A, Rizvi SHM, Hamburg NM. A modern day perspective on smoking in peripheral artery disease. Front Cardiovasc Med. 2023; 10:1154708.View Related Profiles. PMID: 37187787; PMCID: PMC10175606; DOI: 10.3389/fcvm.2023.1154708;
  3. Majid S, Weisbrod RM, Fetterman JL, Keith RJ, Rizvi SHM, Zhou Y, Behrooz L, Robertson RM, Bhatnagar A, Conklin DJ, Hamburg NM. Pod-based e-liquids impair human vascular endothelial cell function. PLoS One. 2023; 18(1):e0280674.View Related Profiles. PMID: 36701344; PMCID: PMC9879485; DOI: 10.1371/journal.pone.0280674;
  4. Behrooz L, Xie W, Goghari A, Robertson RM, Bhatnagar A, Stokes A, Hamburg NM. Electronic Cigarette Use and Chest Pain Report in US Adults. Circulation. 2022; 146(Suppl_1):A10088-A10088.
  5. Behrooz L, Barillas-Lara M, Fattouh M, Loubeau B, Ibrahim M. The role of invasive cardiopulmonary exercise testing in patients with unexplained dyspnea: a systemic review. Acta Cardiol. 2023 Sep; 78(7):754-760.View Related Profiles. PMID: 36345986; DOI: 10.1080/00015385.2022.2141434;
  6. Behrooz L, Ho JE, Hamburg NM. Vascular Aging After COVID-19: A Story of Lasting Injury or Prolonged Healing? Circ Res. 2022 Apr 29; 130(9):1286-1288.View Related Profiles. PMID: 35482837
  7. Majid S, Fetterman J, Weisbrod RM, Behrooz L, Stokes AC, Blaha MJ, Conklin DJ, Srivastava S, Robertson R, Bhatnagar A, Keith R, Hamburg NM. Effects of Pod-Based Electronic Cigarette Use on Vascular Health and Relation to Volatile Organic Compound Exposure in Young Adults. medRxiv. 2022.
  8. Ibrahim M, Behrooz L, Saint Croix GR, Loubeau B, Barillas Lara, MI, Paul L. Epidemiology of Cardiomyopathy in Haitian Patients Seen in a United States Urban, Safety-Net, Academic Medical Center. Circulation. 2021; 144(Suppl_1).
  9. Ibrahim M, Saint Croix GR, Lacy S, Fattouh M, Barillas-Lara MI, Behrooz L, Mechanic O. The use of diflunisal for transthyretin cardiac amyloidosis: a review. Heart Fail Rev. 2022 03; 27(2):517-524.View Related Profiles. PMID: 34272629
  10. Behrooz L, Dilley MA, Petty CR, Huffaker MF, Sheehan WJ, Phipatanakul W. The efficacy of a novel monitoring device on asthma control in children with asthma. Ann Allergy Asthma Immunol. 2020 Sep; 125(3):352-354. PMID: 32574599; PMCID: PMC7483778; DOI: 10.1016/j.anai.2020.06.025;
Showing 10 of 15 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 15 publications over 7 distinct years, with a maximum of 4 publications in 2022


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