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

  • Siddiqi TJ, Rashid AM, Siddiqi AK, Anwer A, Usman MS, Sakhi H, Bhatnagar A, Hamburg NM, Hirsch GA, Rodriguez CJ, Blaha MJ, DeFilippis AP, Benjamin EJ, Hall ME. Association of Electronic Cigarette Exposure on Cardiovascular Health: A Systematic Review and Meta-Analysis. Curr Probl Cardiol. 2023 Sep;48(9):101748. doi: 10.1016/j.cpcardiol.2023.101748. Epub 2023 Apr 22. PMID: 37088177.
  • Posa DK, Miller J, Hoetker D, Ramage MI, Gao H, Zhao J, Doelling B, Bhatnagar A, Wigmore SJ, Skipworth RJE, Baba SP. Skeletal muscle analysis of cancer patients reveals a potential role for carnosine in muscle wasting. J Cachexia Sarcopenia Muscle. 2023 Aug;14(4):1802-1814. doi: 10.1002/jcsm.13258. Epub 2023 May 18. PMID: 37199284; PMCID: PMC10401540.
  • Xie Z, Chen JY, Gao H, Keith RJ, Bhatnagar A, Lorkiewicz P, Srivastava S. Global Profiling of Urinary Mercapturic Acids Using Integrated Library-Guided Analysis. Environ Sci Technol. 2023 Jul 25;57(29):10563-10573. doi: 10.1021/acs.est.2c09554. Epub 2023 Jul 11. PMID: 37432892.
  • Tasdighi E, Jha KK, Dardari ZA, Osuji N, Rajan T, Boakye E, Hall ME, Rodriguez CJ, Stokes AC, El Shahawy O, Benjamin EJ, Bhatnagar A, DeFilippis AP, Blaha MJ. Investigating the association of traditional and non-traditional tobacco product use with subclinical and clinical cardiovascular disease: The Cross-Cohort Collaboration-Tobacco working group rationale, design, and methodology. Tob Induc Dis. 2023 Jul 7;21:89. doi: 10.18332/tid/166517. PMID: 37427074; PMCID: PMC10326890.
  • Lamas GA, Bhatnagar A, Jones MR, Mann KK, Nasir K, Tellez-Plaza M, Ujueta F, Navas-Acien A; American Heart Association Council on Epidemiology and Prevention; Council on Cardiovascular and Stroke Nursing; Council on Lifestyle and Cardiometabolic Health; Council on Peripheral Vascular Disease; and Council on the Kidney in Cardiovascular Disease. Contaminant Metals as Cardiovascular Risk Factors: A Scientific Statement From the American Heart Association. J Am Heart Assoc. 2023 Jul 4;12(13):e029852. doi: 10.1161/JAHA.123.029852. Epub 2023 Jun 12. PMID: 37306302; PMCID: PMC10356104.
  • Boakye E, Erhabor J, Obisesan O, Tasdighi E, Mirbolouk M, Osuji N, Osei AD, Lee J, DeFilippis AP, Stokes AC, Hirsch GA, Benjamin EJ, Robertson RM, Bhatnagar A, El Shahawy O, Blaha MJ. Comprehensive review of the national surveys that assess E-cigarette use domains among youth and adults in the United States. Lancet Reg Health Am. 2023 Jun 7;23:100528. doi: 10.1016/j.lana.2023.100528. PMID: 37497394; PMCID: PMC10366460.
  • Keith RJ, Holm RH, Amraotkar AR, Bezold MM, Brick JM, Bushau-Sprinkle AM, Hamorsky KT, Kitterman KT, Palmer KE, Smith T, Yeager R, Bhatnagar A. Stratified Simple Random Sampling Versus Volunteer Community-Wide Sampling for Estimates of COVID-19 Prevalence. Am J Public Health. 2023 Jul;113(7):768-777. doi: 10.2105/AJPH.2023.307303. Epub 2023 May 18. PMID: 37200600; PMCID: PMC10262242.
  • Ribble A, Hellmann J, Conklin DJ, Bhatnagar A, Haberzettl P. Fine particulate matter (PM2.5)-induced pulmonary oxidative stress contributes to increases in glucose intolerance and insulin resistance in a mouse model of circadian dyssynchrony. Sci Total Environ. 2023 Jun 15;877:162934. doi: 10.1016/j.scitotenv.2023.162934. Epub 2023 Mar 18. PMID: 36934930; PMCID: PMC10164116.
  • Boakye E, Uddin SMI, Osuji N, Meinert J, Obisesan OH, Mirbolouk M, Tasdighi E, El-Shahawy O, Erhabor J, Osei AD, Rajan T, Patatanian M, Holbrook JT, Bhatnagar A, Biswal SS, Blaha MJ. Examining the association of habitual e-cigarette use with inflammation and endothelial dysfunction in young adults: The VAPORS-Endothelial function study. Tob Induc Dis. 2023 Jun 10;21:75. doi: 10.18332/tid/162327. PMID: 37305426; PMCID: PMC10257221.
  • Erhabor J, Boakye E, Osuji N, Obisesan O, Osei AD, Mirbolouk H, Stokes AC, Dzaye O, El-Shahawy O, Rodriguez CJ, Hirsch GA, Benjamin EJ, DeFilippis AP, Robertson RM, Bhatnagar A, Blaha MJ. Psychosocial stressors and current e-cigarette use in the youth risk behavior survey. BMC Public Health. 2023 Jun 6;23(1):1080. doi: 10.1186/s12889-023-16031-w. PMID: 37280552; PMCID: PMC10242777.