Extensive epidemiological and experimental evidence indicates that obesity is a strong and robust risk factor for the development of type 2 diabetes (T2D) and cardiovascular disease (CVD). Numerous studies have also reported strong associations between ambient air particulate matter (PM) and an increased CVD and T2D risk. However, the mechanism(s) by which obesity and exposure to environmental air pollutants increase the risk of T2D and CVD remain unknown. A common feature underlying these pathological states is a damaged endothelium. Endothelial health is maintained with the participation of endothelial progenitor cells (EPCs). The presence of CVD risk factors has been shown to decrease not only the circulating levels of EPCs, but their ability to stimulate tissue repair, as well. The number of circulating EPCs is decreased in patients with T2D. Furthermore, our previous work demonstrates that exposures to environmental air pollutions decrease the number of circulating EPCs and impair vascular VEGF signaling. Therefore, our ongoing research examines the effects of exposures to fine particulate matter (PM2.5) and volatile (e.g. acrolein) air pollutions as well as obesity on EPC levels and function, endothelial health and vascular resistance to insulin and VEGF to investigate changes leading to the progression of the vascular complications and the metabolic syndrome. Results of these studies will not only advance our understanding of the mechanisms by which environmental air pollutions and obesity affect vascular health, but could also lead to the development of new diagnostic and therapeutic strategies for the treatment and management of CVDs and T2D.
- Haberzettl P, O'Toole TE, Bhatnagar A, Conklin DJ. Exposure to Fine Particulate Air Pollution Causes Vascular Insulin Resistance by Inducing Pulmonary Oxidative Stress. Environ Health Perspect. 2016 Apr 29. [Epub ahead of print] PubMed PMID: 27128347.
- Haberzettl P, McCracken JP, Bhatnagar A, Conklin DJ. Insulin sensitizers prevent fine particulate matter-induced vascular insulin resistance and changes in endothelial progenitor cell homeostasis. Am J Physiol Heart Circ Physiol. 2016 Jun 1;310(11):H1423-38. doi: 10.1152/ajpheart.00369.2015. Epub 2016 Mar 25. PubMed PMID: 27016579.
- Haberzettl P, Hill BG. Oxidized lipids activate autophagy in a JNK-dependent manner by stimulating the endoplasmic reticulum stress response. Redox Biol. 2013 Jan 26;1:56-64. doi: 10.1016/j.redox.2012.10.003. eCollection 2013. PubMed PMID: 24024137; PubMed Central PMCID: PMC3757667.
- Haberzettl P, Lee J, Duggineni D, McCracken J, Bolanowski D, O'Toole TE, Bhatnagar A, Conklin DJ. Exposure to ambient air fine particulate matter prevents VEGF-induced mobilization of endothelial progenitor cells from the bone marrow. Environ Health Perspect. 2012 Jun;120(6):848-56. doi: 10.1289/ehp.1104206. Epub 2012 Mar 14. PubMed PMID: 22418586; PubMed Central PMCID: PMC3385427.
- Vladykovskaya E, Sithu SD, Haberzettl P, Wickramasinghe NS, Merchant ML, Hill BG, McCracken J, Agarwal A, Dougherty S, Gordon SA, Schuschke DA, Barski OA, O'Toole T, D'Souza SE, Bhatnagar A, Srivastava S. Lipid peroxidation product 4-hydroxy-trans-2-nonenal causes endothelial activation by inducing endoplasmic reticulum stress. J Biol Chem. 2012 Mar 30;287(14):11398-409. doi: 10.1074/jbc.M111.320416. Epub 2012 Jan 6. PubMed PMID: 22228760; PubMed Central PMCID: PMC3322871.
- Wheat LA, Haberzettl P, Hellmann J, Baba SP, Bertke M, Lee J, McCracken J, O'Toole TE, Bhatnagar A, Conklin DJ. Acrolein inhalation prevents vascular endothelial growth factor-induced mobilization of Flk-1+/Sca-1+ cells in mice. Arterioscler Thromb Vasc Biol. 2011 Jul;31(7):1598-606. doi: 10.1161/ATVBAHA.111.227124. Epub 2011 Apr 28. PubMed PMID: 21527748; PubMed Central PMCID: PMC3182098.
- O'Toole TE, Hellmann J, Wheat L, Haberzettl P, Lee J, Conklin DJ, Bhatnagar A, Pope CA 3rd. Episodic exposure to fine particulate air pollution decreases circulating levels of endothelial progenitor cells. Circ Res. 2010 Jul 23;107(2):200-3. doi: 10.1161/CIRCRESAHA.110.222679. Epub 2010 Jul 1. PubMed PMID: 20595651; PubMed Central PMCID: PMC2943671.
- Haberzettl P, Vladykovskaya E, Srivastava S, Bhatnagar A. Role of endoplasmic reticulum stress in acrolein-induced endothelial activation. Toxicol Appl Pharmacol. 2009 Jan 1;234(1):14-24. doi: 10.1016/j.taap.2008.09.019. Epub 2008 Oct 7. PubMed PMID: 18951912; PubMed Central PMCID: PMC2936103.
- Hill BG, Haberzettl P, Ahmed Y, Srivastava S, Bhatnagar A. Unsaturated lipid peroxidation-derived aldehydes activate autophagy in vascular smooth-muscle cells. Biochem J. 2008 Mar 15;410(3):525-34. PubMed PMID: 18052926.
- Haberzettl P, Schins RP, Höhr D, Wilhelmi V, Borm PJ, Albrecht C. Impact of the FcgammaII-receptor on quartz uptake and inflammatory response by alveolar macrophages. Am J Physiol Lung Cell Mol Physiol. 2008 Jun;294(6):L1137-48. doi: 10.1152/ajplung.00261.2007. Epub 2008 Apr 4. PubMed PMID: 18390832.
- Haberzettl P, Duffin R, Krämer U, Höhr D, Schins RP, Borm PJ, Albrecht C. Actin plays a crucial role in the phagocytosis and biological response to respirable quartz particles in macrophages. Arch Toxicol. 2007 Jul;81(7):459-70. Epub 2007 Mar 21. PubMed PMID: 17375287.