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

• Yeager R, Keith RJ, Riggs DW, Fleischer D, Browning MHEM, Ossola A, Walker KL, Hart JL, Srivastava S, Rai SN, Smith T, Bhatnagar A. Intra-neighborhood associations between residential greenness and blood pressure. Sci Total Environ. 2024 Oct 10;946:173788. doi: 10.1016/j.scitotenv.2024.173788. Epub 2024 Jun 18. PMID: 38901580.
• Jin L, Richardson A, Lynch J, Lorkiewicz P, Srivastava S, Fryar L, Miller A, Theis W, Shirk G, Bhatnagar A, Srivastava S, Riggs DW, Conklin DJ. Formaldehyde and the Transient Receptor Potential Ankyrin-1 Contribute to Electronic Cigarette Aerosol-induced Endothelial Dysfunction in Mice. Toxicol Sci. 2024 Jul 27:kfae096. doi: 10.1093/toxsci/kfae096. Epub ahead of print. PMID: 39067042.
• Ranker LR, Wu J, Hong T, Wijaya D, Benjamin EJ, Bhatnagar A, Robertson RM, Fetterman JL, Xuan Z. Social media use, brand engagement, and tobacco product initiation among youth: Evidence from a prospective cohort study. Addict Behav. 2024 Jul;154:108000. doi: 10.1016/j.addbeh.2024.108000. Epub 2024 Feb 28. PMID: 38461745; PMCID: PMC11135121.
• Xie W, Berlowitz JB, Raquib R, Harlow AF, Benjamin EJ, Bhatnagar A, Stokes AC. Association of cigarette and electronic cigarette use patterns with all-cause mortality: A national cohort study of 145,390 US adults. Prev Med. 2024 May;182:107943. doi: 10.1016/j.ypmed.2024.107943. Epub 2024 Mar 28. PMID: 38552720; PMCID: PMC11039355.
• Keith RJ, Hart JL, Bhatnagar A. Greenspaces And Cardiovascular Health. Circ Res. 2024 Apr 26;134(9):1179-1196. doi: 10.1161/CIRCRESAHA.124.323583. Epub 2024 Apr 25. PMID: 38662868.
• Riggs DW, DuPre NC, James P, Rai SN, Yeager R, Sears CG, Laden F, Bhatnagar A. Association of Ecoregion Distribution of Greenness With Cardiovascular Mortality: A Longitudinal Ecological Study in the United States. Circ Res. 2024 Apr 26;134(9):1221-1223. doi: 10.1161/CIRCRESAHA.124.324427. Epub 2024 Apr 25. PMID: 38662855; PMCID: PMC11047167.
• Kucera C, Ramalingam A, Srivastava S, Bhatnagar A, Carll AP. Nicotine Formulation Influences the Autonomic and Arrhythmogenic Effects of Electronic Cigarettes. Nicotine Tob Res. 2024 Apr 22;26(5):536-544. doi: 10.1093/ntr/ntad237. PMID: 38011908; PMCID: PMC11033561.
• Holm RH, Rempala GA, Choi B, Brick JM, Amraotkar AR, Keith RJ, Rouchka EC, Chariker JH, Palmer KE, Smith T, Bhatnagar A. Dynamic SARS-CoV-2 surveillance model combining seroprevalence and wastewater concentrations for post-vaccine disease burden estimates. Commun Med (Lond). 2024 Apr 9;4(1):70. doi: 10.1038/s43856-024-00494-y. PMID: 38594350; PMCID: PMC11004132.
• Rajagopalan S, Ramaswami A, Bhatnagar A, Brook RD, Fenton M, Gardner C, Neff R, Russell AG, Seto KC, Whitsel LP; American Heart Association Council on Hypertension; Council on Lifestyle and Cardiometabolic Health; Council on Peripheral Vascular Disease; Council on Lifelong Congenital Heart Disease and Heart Health in the Young; Council on Cardiovascular Surgery and Anesthesia; and the American Heart Association Advocacy Coordinating Committee. Toward Heart-Healthy and Sustainable Cities: A Policy Statement From the American Heart Association. Circulation. 2024 Apr 9;149(15):e1067-e1089. doi: 10.1161/CIR.0000000000001217. Epub 2024 Mar 4. Erratum in: Circulation. 2024 Apr 16;149(16):e1129. doi: 10.1161/CIR.0000000000001244. PMID: 38436070.
• Agbonlahor O, DeJarnett N, Hart JL, Bhatnagar A, McLeish AC, Walker KL. Racial/Ethnic Discrimination and Cardiometabolic Diseases: A Systematic Review. J Racial Ethn Health Disparities. 2024 Apr;11(2):783-807. doi: 10.1007/s40615-023-01561-1. Epub 2023 Mar 28. PMID: 36976513; PMCID: PMC10044132.