{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:54:27Z","timestamp":1780473267643,"version":"3.54.1"},"reference-count":44,"publisher":"Wiley","issue":"2-3","license":[{"start":{"date-parts":[[2023,6,11]],"date-time":"2023-06-11T00:00:00Z","timestamp":1686441600000},"content-version":"am","delay-in-days":352,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T00:00:00Z","timestamp":1656028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000104","name":"National Aeronautics and Space Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000104","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microcirculation"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The pathology of snake envenomation is closely tied to the severity of edema in the tissue surrounding the area of the bite. Elucidating the mechanisms that promote the development of such severe edema is critical to a better understanding of how to treat this life\u2010threatening injury. We focused on one of the most abundant venom components in North American viper venom, crotamine, and the effects it has on the cells and function of the lymphatic system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used RT\u2010PCR to identify the location and relative abundance of crotamine's cellular targets (Kv\u03b1 channels) within the tissues and cells of the lymphatic system. We used calcium flux, nitrate production, and cell morphometry to determine the effects of crotamine on lymphatic endothelial cells. We used tracer transport, node morphometry, and node deposition to determine the effects of crotamine on lymph transport in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that genes that encode targets of crotamine are highly present in lymphatic tissues and cells and that there is a differential distribution of those genes that correlates with phasic contractile activity. We found that crotamine potentiates calcium flux in human dermal lymphatic endothelial cells in response to stimulation with histamine and sheer stress (but not alone) and that it alters the production of nitric oxide in response to shear as well as changes the level of F\u2010actin polymerization of those same cells. Crotamine alters lymphatic transport of large molecular weight tracers to local lymph nodes and is deposited within the node mostly in the immediate subcapsular region.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This evidence suggests that snake venom components may have an impact on the function of the lymphatic system. This needs to be studied in greater detail as there are numerous venom components that may have effects on aspects of the lymphatic system. This would not only provide basic information on the pathobiology of snakebite but also provide targets for improved therapeutics to treat snakebite.<\/jats:p><\/jats:sec>","DOI":"10.1111\/micc.12775","type":"journal-article","created":{"date-parts":[[2022,6,11]],"date-time":"2022-06-11T15:49:03Z","timestamp":1654962543000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Effect of the snake venom component crotamine on lymphatic endothelial cell responses and lymph transport"],"prefix":"10.1111","volume":"30","author":[{"given":"Hongjiang","family":"Si","sequence":"first","affiliation":[{"name":"Department of Medical Physiology Texas A&amp;M University Health Science Center  Bryan Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhiu","family":"Yin","sequence":"additional","affiliation":[{"name":"Center for Translational Cancer Research Texas A&amp;M Institute of Biosciences and Technology  Bryan Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology Texas A&amp;M University Health Science Center  Bryan Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Davies","sequence":"additional","affiliation":[{"name":"Center for Translational Cancer Research Texas A&amp;M Institute of Biosciences and Technology  Bryan Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elda","family":"Sanchez","sequence":"additional","affiliation":[{"name":"National Natural Toxins Research Center Texas A&amp;M Kingsville  Kingsville Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montamas","family":"Suntravat","sequence":"additional","affiliation":[{"name":"National Natural Toxins Research Center Texas A&amp;M Kingsville  Kingsville Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Zawieja","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology Texas A&amp;M University Health Science Center  Bryan Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Cromer","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology Texas A&amp;M University Health Science Center  Bryan Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2018.04.016"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.5435\/00124635-201012000-00005"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1081\/CLT-120019127"},{"issue":"1","key":"e_1_2_10_5_1","first-page":"27","article-title":"Snakebite prognostic factors: leading factors of weak therapeutic response following snakebite envenomation","volume":"1","author":"Dadpour B","year":"2012","journal-title":"Asia Pac J Med Toxicol"},{"key":"e_1_2_10_6_1","first-page":"chap 4","volume-title":"Fluid Exchange: Regulation, Functions, and Pathology","author":"Scallan J","year":"2010"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2019.04.006"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.207274"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.208298"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1993.73.1.1"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2009.0007"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2017.0052"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12307"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00664.2015"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00058.2006"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000402"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002722"},{"issue":"4","key":"e_1_2_10_18_1","first-page":"144","article-title":"Lymphatic route of transport and pharmacokinetics of Micrurus fulvius (coral snake) venom in sheep","volume":"45","author":"Paniagua D","year":"2012","journal-title":"Lymphology"},{"issue":"5","key":"e_1_2_10_19_1","first-page":"G602","article-title":"Lymph protein concentration in initial and collecting lymphatics of the rat. Research Support, non\u2010U.S. Gov't Research Support, U.S. Gov't, P.H.S","volume":"252","author":"Zawieja DC","year":"1987","journal-title":"Am J Phys"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-2862(68)90006-X"},{"issue":"2","key":"e_1_2_10_21_1","first-page":"39","article-title":"Electron microscopic study of lymphatic capillaries in the removal of connective tissue fluids and particulate substances","volume":"1","author":"Leak LV","year":"1968","journal-title":"Lymphology"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/01913123.2017.1422827"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.23714"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.112.078188"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12418"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/19336950.2018.1491243"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00499.2017"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-03041-z"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2012.0013"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2011.0014"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032414-112212"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3233"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00744.2014"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.309548"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2016.0062"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12138"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002326"},{"issue":"999","key":"e_1_2_10_38_1","first-page":"536","article-title":"Murine rVEGF164b, an inhibitory VEGF reduces VEGF\u2010A dependent endothelial proliferation and barrier dysfunction. research","volume":"9999","author":"Walter E","year":"2010","journal-title":"Microcirculation."},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-013-9393-2"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020295718728"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.103.6.2379"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1039\/C3SM50798J"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E09-07-0580"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.018473"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.9.9.2561"}],"container-title":["Microcirculation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/micc.12775","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/micc.12775","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/am-pdf\/10.1111\/micc.12775","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/micc.12775","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T05:13:31Z","timestamp":1707714811000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/micc.12775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,24]]},"references-count":44,"journal-issue":{"issue":"2-3","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1111\/micc.12775"],"URL":"https:\/\/doi.org\/10.1111\/micc.12775","archive":["Portico"],"relation":{},"ISSN":["1073-9688","1549-8719"],"issn-type":[{"value":"1073-9688","type":"print"},{"value":"1549-8719","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,24]]},"assertion":[{"value":"2022-04-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12775"}}