Sanjay Srivastava, Ph.D., FAHA

Professor of Medicine; Distinguished University Scholar

Department of Medicine, Division of Cardiovascular Medicine


502-852-5834 sanjay@louisville.edu

Education and Training

Ph.D.: Lucknow University, India
Fellowship: University of Texas Medical Branch at Galveston

Research

Ongoing Projects

Cellular and Molecular Mechanisms of Atherosclerosis: Ongoing studies in Dr. Srivastava's laboratory suggest that that aldehydes generated from oxidized lipids, and as precursors of advanced glycation end products cause endothelial cell and macrophage activation. Concentration of these aldehydes and their protein adducts are significantly increased in vascular pathologies, especially atherosclerosis. His studies suggest that aldehyde-induced endoplasmic reticulum, could at least in parts, be involved in the pathogenesis of vascular complications. His studies also show that oxidized lipids and reactive aldehyde induce the expression of micro RNAs which could induce macrophage apoptosis and necrosis, and affect inflammatory signaling. Dr. Srivastava's laboratory has generated genetically altered mice to examine how (a) regulation of aldehyde metabolizing enzymes or exposure to reagent aldehydes exacerbate atherosclerosis; (b) does quenching of aldehydes by small molecular weight compounds prevents murine atherosclerosis; (c) ER-stress associate inflammatory signaling and apoptosis affect atherosclerosis; and (d) micro RNAs affect atherosclerotic lesion progression and plaque characteristics. To examine the species independent effects, recently he has established new LDL receptor-null rat model of atherosclerosis. The LDL receptor-null rats are also obese and glucose intolerant. Feeding the rats a western diet exacerbates obesity, glucose intolerance and atherosclerosis.


Effects of New and Emerging Tobacco Products on Vascular Toxicity and Inflammation: Another thrust area of Dr. Srivastava's research is to examine the effect of new and emerging tobacco products and their constituents on cardiovascular toxicity and inflammation. He is studying how exposure to electronic nicotine delivery devices such as electronic cigarettes, electronic hookah, and oral tobacco products and their constituents, especially reactive aldehydes such as acrolein and nicotine affect blood platelets, circulating immune cells, endothelial progenitor cells, platelet and endothelial microparticles, vascular functions and athrogenesis.

  • Malovichko M, Zeller I, Krivokhizhina T, Xie Z, Lorkiewicz P, Agarwal A, Wickramasinghe N, Sithu SD, Shah J, O'Toole T, Rai SN, Bhatnagar A, Conklin DJ, Srivastava S. Systemic toxicity of smokeless tobacco products in mice. Nicotine Tobacco Research (in press).
  • Lorkiewicz P, Riggs DW, Keith RJ, Conklin DJ, Xie Z, Sutaria S, Lynch B, Srivastava S, Bhatnagar A. Comparison of Urinary Biomarkers of Exposure in Humans Using Electronic Cigarettes, Combustible Cigarettes, and Smokeless Tobacco. Nicotine Tob Res. 2018 Jun 2. doi: 10.1093/ntr/nty089. [Epub ahead of print] PubMed PMID: 29868926.   https://academic.oup.com/ntr/advance-article/doi/10.1093/ntr/nty089/5032354
  • Conklin DJ, Ogunwale MA, Chen Y, Theis W, Nantz MH, Fu X-A, Chen L-C, Riggs DW, Lorkiewicz P, Bhatnagar A, Srivastava S. Electronic cigarette-generated aldehydes: The contribution of e-liquid components to their formation and the use of urinary aldehyde metabolites as biomarkers of exposure. Aerosol Science and Technology (in press).
  • Keith RJ, Riggs DW, Conklin DJ, Lorkiewicz P, Srivastava S, Bhatnagar A, DeFilippis AP. Nicotine Metabolism in Adults with Type 2 Diabetes. Nicotine Tob Res. 2017 Sep 27. doi: 10.1093/ntr/ntx214. [Epub ahead of print] PubMed PMID:29059414.
  • Conklin DJ, Malovichko MV, Zeller I, Das TP, Krivokhizhina TV, Lynch BH, Lorkiewicz P, Agarwal A, Wickramasinghe N, Haberzettl P, Sithu SD, Shah J, O'Toole TE, Rai SN, Bhatnagar A, Srivastava S. Biomarkers of Chronic Acrolein Inhalation Exposure in Mice: Implications for Tobacco Product-Induced Toxicity. Toxicol Sci. 2017 Aug 1;158(2):263-274. doi: 10.1093/toxsci/kfx095. PubMed PMID: 28482051; PubMed Central PMCID: PMC5837482.
  • Schick SF, Blount BC, Jacob P Rd, Saliba NA, Bernert JT, El Hellani A, Jatlow P, Pappas RS, Wang L, Foulds J, Ghosh A, Hecht SS, Gomez JC, Martin JR, Mesaros C, Srivastava S, St Helen G, Tarran R, Lorkiewicz PK, Blair IA, Kimmel HL, Doerschuk CM, Benowitz NL, Bhatnagar A. Biomarkers of exposure to new and emerging tobacco delivery products. Am J Physiol Lung Cell Mol Physiol. 2017 Sep 1;313(3):L425-L452. doi: 10.1152/ajplung.00343.2016. Epub 2017 May 18. Review. PubMed PMID: 28522563; PubMed Central PMCID: PMC5626373.


Cardiometabolic Toxicity of Volatile Organic Compounds: Apart from lipid oxidation and heating of tobacco products, reactive aldehydes are also abundant in the environment as ubiquitous pollutant and generated as a byproduct of the metabolism of other airborne toxicants such as volatile organic compounds (VOCs). Recently, Dr. Srivastava has established an NIH-funded University of Louisville Superfund Research Center which will study the Cardiometabolic Toxicity of VOCs. Center investigators are conducting mode-of-action research to unravel critical pathways of toxicity and to identify toxicological end-points (cardiometabolic changes) of chemicals (VOCs) found at Superfund and related hazardous waste sites. Using high throughput metabolomic and mass spectrometry approaches, animal experiments and human population studies, Center investigations will aid in the discovery and validation of novel biomarkers of both exposure and cardiometabolic injury that would lay the foundation for future remediation strategies. These studies will employ state-of-the-art tools to develop pollutant atmospheres for animal exposure and to measure unique and sensitive biological endpoints reflective of cardiometabolic injury. Center investigators will create new technologies for detecting VOCs at low environmental levels to enable future exposure assessment activities. Senior Center members will educate and train junior investigators, graduate students and post-doctoral Fellows in the field of environmental science, and promote relevant community awareness and participation to enhance mutual bidirectional understanding of exposure risk and the health effects of exposure. The findings and discoveries of the Center will be transferred to affected communities, end users in public and private sectors, and other stakeholders.