{
    "abstract": "The cardiovascular and pulmonary disease risks of the use of electronic nicotine delivery systems (ENDS) are uncertain. We recently showed that ENDS solvent-derived aerosol (propylene glycol and vegetable glycerin, PG:VG) exposure induced a transient receptor potential ankyrin-1 (TRPA1)-dependent endothelial dysfunction (ED) in healthy female mice. As thermal degradation of PG:VG generates aldehydes, we hypothesized that acrolein (AC), a constituent of ENDS-derived aerosol and a known TRPA1 agonist, was responsible, in part, for the observed TRPA1-dependent pulmonary and vascular effects of PG:VG. To test this, female wild-type (WT) and TRPA1 null mice were exposed by inhalation to either filtered air or AC alone, and biomarkers of exposure and of harm were measured. Compared with their genotype-matched air control group, JUUL Virginia Tobacco (VT), PG:VG, and AC alone exposures (6\u00a0h) significantly increased urinary levels of the AC metabolite, 3-hydroxypropyl mercapturic acid (3HPMA), in both female WT and TRPA1 null mice. AC exposures at 1 and 3\u00a0ppm led to the rapid onset and reversal (upon cessation) of 'respiratory braking' in female WT but not in TRPA1 null mice indicating a TRPA1 dependence. As AC stimulated TRPA1-dependent respiratory braking, we measured urinary monoamines and their metabolites after exposure as a proxy of nervous system activation. In WT mice, AC exposure suppressed levels of dopamine, metanephrine, serotonin (5HT), and 5HT metabolite (5HIAA), whereas in TRPA1 null mice only 5HT was equally suppressed by AC. To assess vascular effects, mice were exposed for 4\u00a0days to Air or AC (6\u00a0h/day, 1\u00a0ppm), and aortic function was measured ex vivo. Although endothelial-dependent relaxation was similar in air control and AC-exposed mice, aortic sensitivity to an NO donor was enhanced significantly and equally by AC in both WT and TRPA1 null mice reflective of a TRPA1-independent and compensatory effect. Collectively, AC exposure at a level present in ENDS aerosols stimulated both TRPA1-dependent and -independent pulmonary, vascular, and systemic effects. These data suggest that ENDS use may increase cardiovascular and pulmonary disease risk, in part, via AC present in ENDS-derived aerosols yet independent of either nicotine or flavorants. The level of AC present in ENDS aerosols should be lowered to an amount where it does not induce biomarkers of vascular, pulmonary, and systemic harm to mitigate potential long-term disease risk.",
    "authors": [
        {
            "affiliation": "American Heart Association-Tobacco Regulation and Addiction Center, University of Louisville, Louisville, KY, USA.\nChristina Lee Brown Envirome Institute, University of Louisville, Louisville, KY, USA.\nCenter for Cardiometabolic Science, University of Louisville, 580 S. Preston Street, Delia Baxter Building, Rm. 404E, Louisville, KY, 40202, USA.",
            "firstname": "Lexiao",
            "initials": "L",
            "lastname": "Jin"
        },
        {
            "affiliation": "Christina Lee Brown Envirome Institute, University of Louisville, Louisville, KY, USA.",
            "firstname": "Andre",
            "initials": "A",
            "lastname": "Richardson"
        },
        {
            "affiliation": "Christina Lee Brown Envirome Institute, University of Louisville, Louisville, KY, USA.\nSuperfund Research Center, University of Louisville, Louisville, KY, USA.",
            "firstname": "Jordan",
            "initials": "J",
            "lastname": "Lynch"
        },
        {
            "affiliation": "American Heart Association-Tobacco Regulation and Addiction Center, University of Louisville, Louisville, KY, USA.\nChristina Lee Brown Envirome Institute, University of Louisville, Louisville, KY, USA.\nCenter for Cardiometabolic Science, University of Louisville, 580 S. Preston Street, Delia Baxter Building, Rm. 404E, Louisville, KY, 40202, USA.",
            "firstname": "Alexis",
            "initials": "A",
            "lastname": "Miller"
        },
        {
            "affiliation": "American Heart Association-Tobacco Regulation and Addiction Center, University of Louisville, Louisville, KY, USA.\nChristina Lee Brown Envirome Institute, University of Louisville, Louisville, KY, USA.\nSuperfund Research Center, University of Louisville, Louisville, KY, USA.\nDepartment of Physiology, University of Louisville, Louisville, KY, 40202, USA.",
            "firstname": "Israel",
            "initials": "I",
            "lastname": "Sithu"
        },
        {
            "affiliation": "American Heart Association-Tobacco Regulation and Addiction Center, University of Louisville, Louisville, KY, USA.\nChristina Lee Brown Envirome Institute, University of Louisville, Louisville, KY, USA.\nDivision of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, KY, USA.\nSuperfund Research Center, University of Louisville, Louisville, KY, USA.",
            "firstname": "Pawel",
            "initials": "P",
            "lastname": "Lorkiewicz"
        },
        {
            "affiliation": "Christina Lee Brown Envirome Institute, University of Louisville, Louisville, KY, USA.\nSuperfund Research Center, University of Louisville, Louisville, KY, USA.",
            "firstname": "Shweta",
            "initials": "S",
            "lastname": "Srivastava"
        },
        {
            "affiliation": "Christina Lee Brown Envirome Institute, University of Louisville, Louisville, KY, USA.\nSuperfund Research Center, University of Louisville, Louisville, KY, USA.",
            "firstname": "Hong",
            "initials": "H",
            "lastname": "Gao"
        },
        {
            "affiliation": "American Heart Association-Tobacco Regulation and Addiction Center, University of Louisville, Louisville, KY, USA.\nChristina Lee Brown Envirome Institute, University of Louisville, Louisville, KY, USA.\nDivision of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, KY, USA.\nSuperfund Research Center, University of Louisville, Louisville, KY, USA.",
            "firstname": "Daniel W",
            "initials": "DW",
            "lastname": "Riggs"
        },
        {
            "affiliation": "American Heart Association-Tobacco Regulation and Addiction Center, University of Louisville, Louisville, KY, USA.\nChristina Lee Brown Envirome Institute, University of Louisville, Louisville, KY, USA.\nDivision of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, KY, USA.\nSuperfund Research Center, University of Louisville, Louisville, KY, USA.",
            "firstname": "Sanjay",
            "initials": "S",
            "lastname": "Srivastava"
        },
        {
            "affiliation": "American Heart Association-Tobacco Regulation and Addiction Center, University of Louisville, Louisville, KY, USA. dj.conklin@louisville.edu.\nChristina Lee Brown Envirome Institute, University of Louisville, Louisville, KY, USA. dj.conklin@louisville.edu.\nDivision of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, KY, USA. dj.conklin@louisville.edu.\nSuperfund Research Center, University of Louisville, Louisville, KY, USA. dj.conklin@louisville.edu.\nCenter for Cardiometabolic Science, University of Louisville, 580 S. Preston Street, Delia Baxter Building, Rm. 404E, Louisville, KY, 40202, USA. dj.conklin@louisville.edu.",
            "firstname": "Daniel J",
            "initials": "DJ",
            "lastname": "Conklin"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.",
    "doi": "10.1007/s12012-025-09978-2\n10.1161/CIRCULATIONAHA.121.057369\n10.1016/j.cjca.2020.12.008\n10.1161/JAHA.119.014570\n10.1016/j.chest.2016.04.012\n10.1152/ajpheart.00307.2020\n10.1152/ajpheart.00591.2018\n10.1093/ntr/ntac019\n10.18001/TRS.6.1.4\n10.1016/j.amjcard.2018.07.029\n10.1161/JAHA.118.009264\n10.1093/toxsci/kfae096\n10.1161/ATVBAHA.122.318051\n10.1016/j.toxrep.2019.02.009\n10.1093/ntr/ntu078\n10.1016/j.ijheh.2016.01.004\n10.1016/j.yrtph.2015.12.019\n10.1093/ntr/ntu174\n10.1021/acsomega.6b00489\n10.1021/tx200536w\n10.1007/s11906-020-01085-7\n10.1016/j.taap.2010.07.013\n10.1093/toxsci/kfx095\n10.1161/ATVBAHA.111.227124\n10.1161/JAHA.114.000934\n10.1016/j.taap.2021.115647\n10.1152/ajpheart.00878.2020\n10.1016/j.taap.2016.08.028\n10.1289/ehp.1003200\n10.1093/toxsci/kfy262\n10.1080/02786826.2018.1500013\n10.1016/j.taap.2020.115120\n10.1016/j.jchromb.2018.09.012\n10.1093/toxsci/kfx095\n10.3389/fphys.2019.00277\n10.1159/000490245\n10.14814/phy2.15120\n10.1113/EP090341\n10.1038/s41467-022-33203-1\n10.1021/acs.chemrestox.1c00328\n10.1016/s0034-5687(01)00234-1\n10.1016/j.taap.2020.115120\n10.1016/j.taap.2020.115012",
    "journal": "Cardiovascular toxicology",
    "keywords": [
        "Aldehyde",
        "ENDS",
        "Endothelial dysfunction",
        "Irritants",
        "Respiratory braking",
        "TRPA1",
        "Tobacco"
    ],
    "methods": null,
    "publication_date": "2025-02-26",
    "pubmed_id": "40000582\n35514292\n33338608\n32345096\n27108682\n32734819\n30707616\n35100430\n31930162\n30170691\n30021806\n39067042\n36288292\n14971480\n30886823\n24832759\n26847410\n26743740\n25187061\n28393137\n22352345\n32857217\n20678513\n28482051\n21527748\n25099132\n34271065\n19270193\n33543686\n16564016\n19074743\n27592100\n21377951\n30351402\n18568077\n31456604\n32634517\n30248561\n28482051\n30984013\n29975955\n34755498\n35661445\n36284091\n35044764\n11504582\n32634517\n32320793\n8531969",
    "results": null,
    "title": "Role of the Transient Receptor Potential Ankyrin-1 in the Pulmonary, Vascular, and Systemic Effects of Short-Term Acrolein Inhalation in Mice: Implications for the Toxicity of Electronic Nicotine Delivery Systems.",
    "xml": "<Element 'PubmedArticle' at 0x788505478d60>"
}