Aruni Bhatnagar, Ph.D., FAHA

Professor of Medicine
Chief, Division of Environmental Medicine
Vice Chair for Research
Smith and Lucille Gibson Professor of Medicine
Director, Christina Lee Brown Envirome Institute/
American Heart Association Tobacco Regulation Center
Distinguished University Scholar

502-852-5966 Email

Education and Training

Ph.D.: University of Kanpur, Chemistry
Postdoctoral Fellowship: University of Texas Medical Branch at Galveston

Research Interests

The major focus of our research is to elucidate the mechanisms by which oxidative stress affects cardiovascular function. In particular, we are interested in the role of lipid peroxidation as a contributor to myocardial ischemic injury and atherosclerosis. Although lipid peroxidation generates several reactive intermediates and end products, lipid-derived unsaturated aldehydes are believed to be a major source of oxidative stress and these toxicants appear to be critical mediators of tissue injury due to lipid peroxidation. In order to understand how the cardiovascular tissues protect themselves from the toxic products of lipid peroxidation, we are currently investigating the biochemical mechanisms by which unsaturated aldehydes are detoxified in the heart and blood vessels. We have learned that the enzymes - aldose reductase, glutathione S-transferases and aldehyde dehydrogenase are the major constituents of aldehyde metabolism in the heart, and vascular smooth muscle and endothelial cells, and that these enzymes function in tandem to protect cardiovascular tissues from the harmful effects of lipid peroxidation. Based on this understanding we are currently assessing in detail the role of aldose reductase and related aldo-keto reductases in the detoxification of lipid peroxidation products. We are investigating whether inhibition or upregulation of these enzymes affects the ability of the heart to withstand oxidative stress during ischemia and reperfusion. In a parallel series of experiments we are studying the role of aldose reductase in atherogenesis in an effort to ascertain whether changes in aldehyde metabolism alter plaque burden in atherosclerotic animals. We believe that this line of inquiry will lead to a better understanding of the mechanisms by which oxidative stress mediates or exacerbates cardiovascular disease, and how the untoward cardiovascular effects of lipid peroxidation could be prevented.

In addition to the metabolism and detoxification of endogenous aldehydes, our research interests also include cardiovascular toxicity of environmental aldehydes. Several ubiquitous pollutants such as gasoline vapor, car exhaust, smoke, and smog contain significant amounts of reactive aldehydes. Similar aldehydes are also generated during the metabolism of pollutants such as butadiene, vinyl chloride and allylamine and cardiotoxic drugs such as cylcophosphamide and adriamycin. These aldehydes are related, in structure and toxicity, to those generated endogenously during lipid peoxidation. Thus, our work on the lipid peroxidation-derived aldehydes bears significance for understanding the cardiovascular effects of environmental aldehydes. To examine this rigorously, we have recently initiated a series of studies to test whether environmental exposure to aldehydes exacerbates atherosclerosis and induces myocardial dysfunction, and whether aldehyde exposure is a risk factor for the development of heart disease.

Featured Publications

  • Faleye TOC, Driver EM, Bowes DA, Holm RH, Talley D, Yeager R, Bhatnagar A, Smith T, Varsani A, Halden RU, Scotch M. Detection of human, porcine and canine picornaviruses in municipal sewage sludge using pan-enterovirus amplicon-based long-read Illumina sequencing. Emerg Microbes Infect. 2022 Dec;11(1):1339-1342. doi: 10.1080/22221751.2022.2071173. PMID: 35475464; PMCID: PMC9132413.
  • Coleman CJ, Yeager RA, Pond ZA, Riggs DW, Bhatnagar A, Arden Pope C 3rd. Mortality risk associated with greenness, air pollution, and physical activity in a representative U.S. cohort. Sci Total Environ. 2022 Jun 10;824:153848. doi: 10.1016/j.scitotenv.2022.153848. Epub 2022 Feb 14. PMID: 35176374.
  • Boakye E, Obisesan OH, Uddin SMI, El-Shahawy O, Dzaye O, Osei AD, Benjamin EJ, Stokes AC, Robertson RM, Bhatnagar A, Blaha MJ. Corrigendum to "Cannabis vaping among adults in the United States: Prevalence, trends, and association with high-risk behaviors and adverse respiratory conditions" [Preventive Medicine 153 (2021) 106800]. Prev Med. 2022 Jun;159:107052. doi: 10.1016/j.ypmed.2022.107052. Epub 2022 Apr 18. Erratum for: Prev Med. 2021 Dec;153:106800. PMID: 35450724.
  • Xie W, Tackett AP, Berlowitz JB, Harlow AF, Kathuria H, Galiatsatos P, Fetterman JL, Cho J, Blaha MJ, Hamburg NM, Robertson RM, DeFilippis AP, Hall ME, Bhatnagar A, Benjamin EJ, Stokes AC. Association of Electronic Cigarette Use with Respiratory Symptom Development among U.S. Young Adults. Am J Respir Crit Care Med. 2022 Jun 1;205(11):1320-1329. doi: 10.1164/rccm.202107-1718OC. PMID: 35089853.
  • Berlowitz JB, Xie W, Harlow AF, Hamburg NM, Blaha MJ, Bhatnagar A, Benjamin EJ, Stokes AC. E-Cigarette Use and Risk of Cardiovascular Disease: A Longitudinal Analysis of the PATH Study (2013-2019). Circulation. 2022 May 17;145(20):1557-1559. doi: 10.1161/CIRCULATIONAHA.121.057369. Epub 2022 May 6. PMID: 35514292.
  • Dwenger MM, Raph SM, Reyzer ML, Lisa Manier M, Riggs DW, Wohl ZB, Ohanyan V, Mack G, Pucci T, Moore JB 4th, Hill BG, Chilian WM, Caprioli RM, Bhatnagar A, Nystoriak MA. Pyridine nucleotide redox potential in coronary smooth muscle couples myocardial blood flow to cardiac metabolism. Nat Commun. 2022 Apr 19;13(1):2051. doi: 10.1038/s41467-022-29745-z. PMID: 35440632; PMCID: PMC9018695.
  • Lorkiewicz P, Keith R, Lynch J, Jin L, Theis W, Krivokhizhina T, Riggs D, Bhatnagar A, Srivastava S, Conklin DJ. Electronic Cigarette Solvents, JUUL E-Liquids, and Biomarkers of Exposure: In Vivo Evidence for Acrolein and Glycidol in E-Cig-Derived Aerosols. Chem Res Toxicol. 2022 Feb 21;35(2):283-292. doi: 10.1021/acs.chemrestox.1c00328. Epub 2022 Jan 19. PMID: 35044764; PMCID: PMC8864610.
  • Riggs DW, Malovichko MV, Gao H, McGraw KE, Taylor BS, Krivokhizhina T, Rai SN, Keith RJ, Bhatnagar A, Srivastava S. Environmental exposure to volatile organic compounds is associated with endothelial injury. Toxicol Appl Pharmacol. 2022 Feb 15;437:115877. doi: 10.1016/j.taap.2022.115877. Epub 2022 Jan 16. PMID: 35045333.
  • Cohen JE, Krishnan-Sarin S, Eissenberg T, Gould TJ, Berman ML, Bhatnagar A, Barnett TE, Soule E, Popova L, Tan ASL, Blank MD, Ling PM, O'Connor R. Balancing Risks and Benefits of E-Cigarettes in the Real World. Am J Public Health. 2022 Feb;112(2):e1-e2. doi: 10.2105/AJPH.2021.306607. PMID: 35080942; PMCID: PMC8802586.Bhatnagar A. Cardiovascular Effects of Particulate Air Pollution. Annu Rev Med. 2022 Jan 27;73:393-406. doi: 10.1146/annurev-med-042220-011549. Epub 2021 Oct 13. PMID: 34644154.