{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:58:14Z","timestamp":1792022294684,"version":"4.4.0"},"reference-count":102,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Cardiac involvement in systemic sclerosis (SSc) is mechanistically heterogeneous, driven by concurrently operative processes spanning right ventricular dysfunction, pulmonary microvascular remodeling, and mitochondrial damage. The existing literature rarely synthesizes these domains simultaneously, leaving substantive gaps in mechanistic understanding and the clinical management of SSc cardiac disease. An integrative review of original primary research was conducted using PubMed, Scopus, and Web of Science. Search terms combined \u201csystemic sclerosis,\u201d \u201cright ventricular dysfunction,\u201d \u201cechocardiographic strain,\u201d \u201cpulmonary microvascular disease,\u201d \u201cnailfold capillaroscopy,\u201d \u201cmitochondrial dysfunction,\u201d \u201coxidative stress,\u201d and \u201ccardiac biomarkers.\u201d Eligible articles were required to report original empirical findings in SSc or SSc-related pulmonary arterial hypertension populations, encompassing echocardiographic, microvascular, molecular, or biomarker outcomes. Right ventricular function is compromised across multiple echocardiographic dimensions\u2014from an elevated myocardial performance index and impaired ventriculoarterial coupling to prognostically significant speckle-tracking strain abnormalities\u2014independent of overt pulmonary hypertension. Pulmonary microvascular disease, quantified by nailfold capillaroscopy and flow-mediated dilation, correlates directly with cardiac magnetic resonance tissue characterization in SSc-related pulmonary arterial hypertension. Mitochondrial dysfunction involving respiratory chain impairment, abnormal fusion dynamics, and altered mitochondrial DNA (mtDNA)copy number is demonstrable across dermal fibroblasts, monocytes, and immune cell populations. Circulating cardiac biomarkers complement echocardiographic findings and predict cardiopulmonary mortality. The integrative framework linking right ventricular remodeling, peripheral vasculopathy, and mitochondrial injury offers substantially richer insight into SSc cardiac pathophysiology than any single-domain perspective can provide, with direct implications for early detection and therapeutic targeting.<\/jats:p>","DOI":"10.3390\/ijms27177683","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T12:03:43Z","timestamp":1787832223000},"page":"7683","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mitochondrial Dysregulation and Molecular Signaling in Systemic Sclerosis Cardiac Disease: An Integrative Echocardiographic, Microvascular, and Biomarker Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7715-6941","authenticated-orcid":false,"given":"Francesca","family":"Coppi","sequence":"first","affiliation":[{"name":"Department of Medical and 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5244-0802","authenticated-orcid":false,"given":"Francesco","family":"Sbarra","sequence":"additional","affiliation":[{"name":"Cardiology Unit of Emergency Department, Guglielmo da Saliceto Hospital, 29121 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damiano","family":"De Cesare","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5161-5358","authenticated-orcid":false,"given":"Francesco","family":"Marangi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, 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