{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T23:24:47Z","timestamp":1772753087991,"version":"3.50.1"},"reference-count":77,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,2,27]],"date-time":"2009-02-27T00:00:00Z","timestamp":1235692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>KCNJ11<\/jats:italic> null mutants, lacking Kir6.2 ATP\u2010sensitive K<jats:sup>+<\/jats:sup> (K<jats:sub>ATP<\/jats:sub>) channels, exhibit a marked susceptibility towards hypertension (HTN)\u2010induced heart failure. To gain insight into the molecular alterations induced by knockout of this metabolic sensor under hemodynamic stress, wild\u2010type (WT) and Kir6.2 knockout (Kir6.2\u2010KO) cardiac proteomes were profiled by comparative 2\u2010DE and Orbitrap MS. Despite equivalent systemic HTN produced by chronic hyperaldosteronism, 114 unique proteins were altered in Kir6.2\u2010KO compared to WT hearts. Bioinformatic analysis linked the primary biological function of the K<jats:sub>ATP<\/jats:sub> channel\u2010dependent protein cohort to energetic metabolism (64% of proteins), followed by signaling infrastructure (36%) including oxidoreductases, stress\u2010related chaperones, processes supporting protein degradation, transcription and translation, and cytostructure. Mapped protein\u2013protein relationships authenticated the primary impact on metabolic pathways, delineating the K<jats:sub>ATP<\/jats:sub> channel\u2010dependent subproteome within a nonstochastic network. Iterative systems interrogation of the proteomic web prioritized heart\u2010specific adverse effects, <jats:italic>i.e<\/jats:italic>., \u201cCardiac Damage\u201d, \u201cCardiac Enlargement\u201d, and \u201cCardiac Fibrosis\u201d, exposing a predisposition for the development of cardiomyopathic traits in the hypertensive Kir6.2\u2010KO. Validating this maladaptive forecast, phenotyping documented an aggravated myocardial contractile performance, a massive interstitial fibrosis and an exaggerated left ventricular size, all prognostic indices of poor outcome. Thus, Kir6.2 ablation engenders unfavorable proteomic remodeling in hypertensive hearts, providing a composite molecular substrate for pathologic stress\u2010associated cardiovascular disease.<\/jats:p>","DOI":"10.1002\/pmic.200800718","type":"journal-article","created":{"date-parts":[[2009,2,27]],"date-time":"2009-02-27T06:38:02Z","timestamp":1235716682000},"page":"1314-1325","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Proteomic profiling of K<sub>ATP<\/sub> channel\u2010deficient hypertensive heart maps risk for maladaptive cardiomyopathic outcome"],"prefix":"10.1002","volume":"9","author":[{"given":"Jelena","family":"Zlatkovic","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. 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