{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T05:08:19Z","timestamp":1784092099112,"version":"3.55.0"},"reference-count":88,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001824","name":"Grantov\u00e1 Agentura \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>The conventional approach to studying hypertension and cardiac hypertrophy primarily focuses on electrochemical signaling mediated by gap junctions. However, mechanical adherens junctions also contribute to hypertrophy through activation of \u03b2-catenin, promoting transcription of growth-inducing genes. Pyridostigmine reduces heart rate, whereas trandolapril is clinically employed as an antihypertensive agent. In this study, we investigated the impact of both drugs on the cardiac phosphoproteome of hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Label-free LC\u2013MS quantification was used to identify alterations in biological processes and cellular compartments. Both agents induced changes in the phosphorylation of proteins associated with adherens junctions, desmosomes, the mitochondrial electron transport chain, and metabolic pathways, each displaying distinct drug-specific patterns. Our data indicate that adaptive remodeling in hypertensive hearts is largely governed by phosphorylation-mediated regulation of the entire area composita, particularly adherens and desmosomal junctions, highlighting the crucial role of mechanical junctions in addition to electrochemical signaling. The observed ability of trandolapril to restore phosphorylation of junctional proteins, which may contribute to the suppression of cardiac hypertrophy, underscores the importance of preserving cardiomyocyte mechanical stability in the management of hypertension-related pathologies.<\/jats:p>","DOI":"10.3389\/fmolb.2026.1858563","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:45:27Z","timestamp":1784090727000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Regulation of mechanical intercellular junctions and components of the mitochondrial electron transport chain and the TCA cycle in the hypertrophic heart by pyridostigmine or trandolapril"],"prefix":"10.3389","volume":"13","author":[{"given":"Zdenka","family":"Drastichova","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Science, Charles University","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Hejnova","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Science, Charles University","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almos","family":"Boro\u0161","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Czech Academy of Sciences","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Behuliak","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Czech Academy of Sciences","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiri","family":"Novotny","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Science, Charles University","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.3390\/biomedicines10071707","article-title":"Cardiac Cx43 signaling is enhanced and TGF-beta1\/SMAD2\/3 suppressed in response to cold acclimation and modulated by thyroid status in hairless SHR(M)","volume":"10","author":"Andelova","year":"2022","journal-title":"Biomedicines"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.3390\/biom14121509","article-title":"Acclimation of hairless spontaneously hypertensive rat to ambient temperature attenuates hypertension-induced pro-arrhythmic downregulation of Cx43 in the left heart ventricle of males","volume":"14","author":"Andelova","year":"2024","journal-title":"Biomolecules"},{"key":"B3","doi-asserted-by":"publisher","first-page":"102838","DOI":"10.1016\/j.jbc.2022.102838","article-title":"Regulation and function of the mammalian tricarboxylic acid cycle","volume":"299","author":"Arnold","year":"2023","journal-title":"J. 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