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We showed that 4,6\u2010sulfation of CSPGs was critical for preventing nerve growth into the scar. Promoting early reinnervation with therapeutics reduces arrhythmias during the first 2\u2009weeks after MI, but the longer\u2010term consequences of restoring innervation are unknown. Therefore, we asked if the beneficial effects of early reinnervation were sustained. We compared cardiac function and arrhythmia susceptibility 40\u2009days after MI in mice treated on Days 3\u201310 with vehicle or with intracellular sigma peptide to restore innervation. Surprisingly, both groups had normal innervation density in the cardiac scar 40\u2009days after MI, indicating delayed reinnervation of the infarct in vehicle\u2010treated mice. That coincided with similar cardiac function and arrhythmia susceptibility in the two groups. We investigated the mechanism allowing delayed reinnervation of the cardiac scar. We found that CSPG 4,6\u2010sulfation, which is elevated early after ischemia\u2013reperfusion, was reduced to control levels allowing reinnervation of the infarct. Thus, remodeling of extracellular matrix weeks after injury leads to remodeling of sympathetic neurons in the heart.<\/jats:p>","DOI":"10.14814\/phy2.15702","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T04:54:44Z","timestamp":1684990484000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Loss of chondroitin sulfate proteoglycan sulfation allows delayed sympathetic reinnervation after cardiac ischemia\u2013reperfusion"],"prefix":"10.14814","volume":"11","author":[{"given":"Matthew R.","family":"Blake","sequence":"first","affiliation":[{"name":"Department of Chemical Physiology and Biochemistry Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana C.","family":"Parrish","sequence":"additional","affiliation":[{"name":"Department of Chemical Physiology and Biochemistry Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie A.","family":"Staffenson","sequence":"additional","affiliation":[{"name":"Department of Chemical Physiology and Biochemistry Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Neurology Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Woodward","sequence":"additional","affiliation":[{"name":"Department of Chemical Physiology and Biochemistry Oregon Health and Science University  Portland Oregon USA"},{"name":"Department of Neurology Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4658-8730","authenticated-orcid":false,"given":"Beth A.","family":"Habecker","sequence":"additional","affiliation":[{"name":"Department of Chemical Physiology and Biochemistry Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.1c00854"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.78387"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.12.066"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.04.008"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-005-0144-6"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1128-2"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.93.9.1667"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.07.096"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30467-5"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5866-12.2013"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7235"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2005.04.006"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.09.054"},{"key":"e_1_2_9_15_1","first-page":"707","article-title":"The autonomic nervous system and cardiac arrhythmias: Current concepts and emerging therapies. 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