{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:41:46Z","timestamp":1785436906448,"version":"3.56.0"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Anhui Provincial Department of Education","award":["GXXT-2020-024"],"award-info":[{"award-number":["GXXT-2020-024"]}]},{"award":["GXXT-2020-024"],"award-info":[{"award-number":["GXXT-2020-024"]}],"id":[{"id":"https:\/\/ror.org\/012m7k033","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Anhui University Collaborative Innovation Project","award":["GXXT-2020-024"],"award-info":[{"award-number":["GXXT-2020-024"]}]},{"name":"2024 Enterprise Attachment Practice Program for Science and Engineering Teachers of Anhui Provincial Universities","award":["2025jsqygz59"],"award-info":[{"award-number":["2025jsqygz59"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Aims: Coronary heart disease (CHD) associated with rheumatoid arthritis (RA) is a primary driver of mortality in RA patients. In this study, we sought to establish a combined rat model of CHD and RA by integrating cardiac ischemia\/reperfusion (I\/R), high-fat diet (HFD), and intradermal administration of bovine type II collagen emulsified in complete Freund\u2019s adjuvant. The aim of constructing this model is to investigate and analyze the pathogenesis of RA-induced CHD under the modulation of HFD and cardiac I\/R exposure. Methods and Results: Sixty-four male Sprague\u2013Dawley rats were randomly categorized into eight groups (n = 8 per group): control, I\/R, HFD, collagen-induced arthritis (CIA), I\/R + CIA, HFD + CIA, I\/R + HFD, and I\/R + HFD + CIA groups (n = 8 per group). We applied Synchrotron radiation-based X-ray micro-computed tomography (micro-CT) to observe the structural changes within the model over time. To further elucidate molecular mechanisms, transcriptome RNA-seq analysis was carried out to identify key signaling pathways, with particular emphasis on the homeostasis of Toll-like receptor 4 (TLR4)\/Myd88 signaling in the ischemic myocardium. Furthermore, we conducted in vivo shRNA-mediated knockdown of polymerase I and transcription release factor (PTRF) and evaluated the co-localization of PTRF and TLR4 through immunofluorescence experiments. It is worth mentioning that our rat model of RA-induced (CHD) under a high-fat diet effectively manifested the relevant pathological features that align with the Traditional Chinese Medicine (TCM) definition of \u201cbi\u201d syndrome. The results indicate that the combined stimulation of HFD and CIA significantly elevated cardiac injury markers (CK-MB, LDH, CRP, and c-TNT) and was accompanied by a more severe expansion of the infarct area and increased cardiomyocyte apoptosis compared to the I\/R group alone. In addition, the histopathological evaluation revealed significantly aggravated myocardial inflammation and fibrosis deposition, accompanied by extensive areas of tissue damage, further indicating a state of heightened inflammation and severe cardiac degenerative changes. Consistently, myocardial tissues from rats in the I\/R + CIA + HFD group exhibited robust activation of the TLR4\/MyD88 signaling pathway and a pronounced elevation in the p-JNK\/JNK ratio. Moreover, pronounced co-localization between PTRF and TLR4 was evident in small vessels surrounding the infarcted myocardium. Importantly, AAV-mediated knockdown of PTRF attenuated the HFD- and CIA-induced exacerbation of myocardial injury in I\/R rats. Conclusions: We successfully established a rat model of CHD with rheumatic syndrome using I\/R in combination with RA and HFD. The present findings suggest that the PTRF-related TLR4\/MyD88-JNK signaling pathway may act as an important regulatory mechanism underlying myocardial injury aggravated by combined HFD and CIA stimulation.<\/jats:p>","DOI":"10.3390\/biom16050753","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T12:14:52Z","timestamp":1779452092000},"page":"753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Compound Augmentation of Myocardial Injury in a Rat Model of Coronary Heart Disease Induced by Ischemia\/Reperfusion, Rheumatoid Arthritis, and High-Fat Diet: A Molecular Mechanistic Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7848-5130","authenticated-orcid":false,"given":"Qixiang","family":"Xu","sequence":"first","affiliation":[{"name":"Provincial Engineering Laboratory for Screening and Re-Evaluation of Active Compounds of Herbal Medicines in Southern Anhui, Wannan Medical University, Wuhu 241002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2404-058X","authenticated-orcid":false,"given":"Jin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4552-0087","authenticated-orcid":false,"given":"Lvming","family":"Li","sequence":"additional","affiliation":[{"name":"Provincial Engineering Laboratory for Screening and Re-Evaluation of Active Compounds of Herbal Medicines in Southern Anhui, Wannan Medical University, Wuhu 241002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0085-0345","authenticated-orcid":false,"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Provincial Engineering Laboratory for Screening and Re-Evaluation of Active Compounds of Herbal Medicines in Southern Anhui, Wannan Medical University, Wuhu 241002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4105-901X","authenticated-orcid":false,"given":"Zui","family":"Pan","sequence":"additional","affiliation":[{"name":"Bone-Muscle Research Center, College of Nursing and Health Innovation, The University of Texas at Arlington, Arlington, TX 76019, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4916-4829","authenticated-orcid":false,"given":"Yongqiu","family":"Zheng","sequence":"additional","affiliation":[{"name":"Provincial Engineering Laboratory for Screening and Re-Evaluation of Active Compounds of Herbal Medicines in Southern Anhui, Wannan Medical University, Wuhu 241002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"118671","DOI":"10.1016\/j.jep.2024.118671","article-title":"Mesua Assamica (King & Prain) Kosterm. 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