{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:49:05Z","timestamp":1790963345983,"version":"4.1.0"},"reference-count":43,"publisher":"American Physiological Society","issue":"4","funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences (NIGMS)","doi-asserted-by":"publisher","award":["GM103492"],"award-info":[{"award-number":["GM103492"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["HL122676"],"award-info":[{"award-number":["HL122676"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association (AHA)","doi-asserted-by":"publisher","award":["16SDG27260070"],"award-info":[{"award-number":["16SDG27260070"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"HHS | NIH | National Institute of Environmental Health Sciences (NIEHS)","doi-asserted-by":"publisher","award":["ES023716"],"award-info":[{"award-number":["ES023716"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2019,4,1]]},"abstract":"<jats:p> Myocardial ischemia-reperfusion (I\/R) results in the generation of free radicals, accumulation of lipid peroxidation-derived unsaturated aldehydes, variable angina (pain), and infarction. The transient receptor potential ankyrin 1 (TRPA1) mediates pain signaling and is activated by unsaturated aldehydes, including acrolein and 4-hydroxynonenal. The contribution of TRPA1 (a Ca<jats:sup>2+<\/jats:sup>-permeable channel) to I\/R-induced myocardial injury is unknown. We tested the hypothesis that cardiac TRPA1 confers myocyte sensitivity to aldehyde accumulation and promotes I\/R injury. Although basal cardiovascular function in TRPA1-null mice was similar to that in wild-type (WT) mice, infarct size was significantly smaller in TRPA1-null mice than in WT mice (34.1\u2009\u00b1\u20099.3 vs. 14.3\u2009\u00b1\u20099.9% of the risk region, n = 8 and 7, respectively, P &lt; 0.05), despite a similar I\/R-induced area at risk (40.3\u2009\u00b18.4% and 42.2\u2009\u00b1\u200911.3% for WT and TRPA1-null mice, respectively) after myocardial I\/R (30 min of ischemia followed by 24 h of reperfusion) in situ. Positive TRPA1 immunofluorescence was present in murine and human hearts and was colocalized with connexin43 at intercalated disks in isolated murine cardiomyocytes. Cardiomyocyte TRPA1 was confirmed by quantitative RT-PCR, DNA sequencing, Western blot analysis, and electrophysiology. A role of TRPA1 in cardiomyocyte toxicity was demonstrated in isolated cardiomyocytes exposed to acrolein, an I\/R-associated toxin that induces Ca<jats:sup>2+<\/jats:sup> accumulation and hypercontraction, effects significantly blunted by HC-030031, a TRPA1 antagonist. Protection induced by HC-030031 was quantitatively equivalent to that induced by SN-6, a Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup> exchange inhibitor, further supporting a role of Ca<jats:sup>2+<\/jats:sup> overload in acrolein-induced cardiomyocyte toxicity. These data indicate that cardiac TRPA1 activation likely contributes to I\/R injury and, thus, that TRPA1 may be a novel therapeutic target for decreasing myocardial I\/R injury. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY Transient receptor potential ankyrin 1 (TRPA1) activation mediates increased blood flow, edema, and pain reception, yet its role in myocardial ischemia-reperfusion (I\/R) injury is unknown. Genetic ablation of TRPA1 significantly decreased myocardial infarction after I\/R in mice. Functional TRPA1 in cardiomyocytes was enriched in intercalated disks and contributed to acrolein-induced Ca<jats:sup>2+<\/jats:sup> overload and hypercontraction. These data indicate that I\/R activation of TRPA1 worsens myocardial infarction; TRPA1 may be a potential target to mitigate I\/R injury. <\/jats:p>","DOI":"10.1152\/ajpheart.00106.2018","type":"journal-article","created":{"date-parts":[[2019,2,8]],"date-time":"2019-02-08T14:53:27Z","timestamp":1549637607000},"page":"H889-H899","source":"Crossref","is-referenced-by-count":58,"title":["TRPA1 channel contributes to myocardial ischemia-reperfusion injury"],"prefix":"10.1152","volume":"316","author":[{"given":"Daniel J.","family":"Conklin","sequence":"first","affiliation":[{"name":"Diabetes and Obesity Center, University of Louisville, Louisville, Kentucky"},{"name":"Envirome Institute, University of Louisville, Louisville, Kentucky"},{"name":"Department of Medicine, University of Louisville, Louisville, Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiru","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cardiology, University 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