{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:44:14Z","timestamp":1788997454153,"version":"build-2803163510"},"reference-count":104,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Climate change has transformed extreme heat from a transient environmental perturbation into a persistent threat that worsens cardiovascular outcomes. Epidemiological studies show a lag between heat exposure and peaks in acute myocardial infarction (AMI) mortality, indicating a subclinical, latent vulnerability. This latent vulnerability likely originates at the level of the microvasculature, as cardiac microvascular endothelial cells (CMECs)\u2014the heart\u2019s primary \u201cthermal sensors\u201d\u2014are uniquely susceptible to proteotoxic stress. The existing literature suggests that this sensitivity may be mediated by thermodynamically gated activation of the activating transcription factor 6 (ATF6) branch of the unfolded protein response (UPR), which could function as a master switch that reprograms endothelial cells from a pro-repair to a maladaptive, anti-angiogenic phenotype. However, this mechanism is derived primarily from preclinical studies and lacks direct validation in humans. The resulting \u201cendothelial memory\u201d is sustained by epigenetic modifications and organelle uncoupling; it persists beyond the initial insult and impairs subsequent neovascularization. As a result, ischemia occurs later in a compromised microenvironment, promoting a fibrosis\u2013conduction mismatch that drives infarct expansion and arrhythmic risk. Thus, the post-exposure latent phase emerges as a novel therapeutic window: Precision targeting of the ER stress\u2013angiogenesis axis during this period offers a focused strategy to protect heat-vulnerable individuals<\/jats:p>","DOI":"10.3390\/ijms27073186","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T16:34:08Z","timestamp":1774974848000},"page":"3186","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Linking Heat Stress to Impaired Cardiac Repair: The ER Stress\u2013Angiogenesis Axis as a Critical Barrier"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1095-6439","authenticated-orcid":false,"given":"Tao","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu 640041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu 640041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu 640041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2950","DOI":"10.1093\/eurheartj\/ehaf326","article-title":"Heat extremes and cardiovascular diseases: A scientific statement of the Association of Cardiovascular Nursing & Allied Professions, Association for Acute Cardiovascular Care, European Association of Preventive Cardiology, Heart Failure Association, European Heart Rhythm Association of the ESC, the ESC Council on Hypertension, the ESC Council on Stroke, and the ESC Working Group on Cardiovascular Pharmacotherapy","volume":"46","author":"Chaseling","year":"2025","journal-title":"Eur. 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