Integrative molecular pathology of sudden cardiac death associated with ARVC-like cardiomyopathy in a Western Lowland Gorilla

Abstract Background Cardiovascular disease is a major cause of morbidity and mortality in captive great apes, however, the molecular basis of sudden cardiac death (SCD) in gorillas remains poorly characterized. In particular, few studies have integrated histopathology with genomic, transcriptional, and protein-level analyses in non-human primate cardiomyopathy. Objective This study aimed to characterize the pathological and molecular features of sudden cardiac death associated with arrhythmogenic right ventricular cardiomyopathy (ARVC)-like myocardial remodeling in a Western lowland gorilla. Methods A 28-year-old male Western lowland gorilla that died suddenly after mild nonspecific clinical signs was examined by necropsy and histopathology. Whole-genome sequencing was performed using cardiac tissue, followed by functional variant annotation and Gene Ontology enrichment analysis. To support the genomic findings, qRT-PCR and western blot analyses were performed for fibrosis-, desmosome-, extracellular matrix remodeling-, and myocardial injury-associated markers. Results Gross examination revealed cardiomegaly, epicardial adiposity, hemopericardium, and reduced myocardial elasticity. Histologically, the right ventricular myocardium showed extensive interstitial fibrosis and multifocal fatty infiltration, consistent with ARVC-like myocardial remodeling. WGS identified functional variants in genes associated with cardiac remodeling and ARVC-related pathways, including genes involved in desmosomal integrity, sarcomeric structure, and extracellular matrix regulation. GO enrichment analysis demonstrated significant association with cardiac muscle contraction, desmosome organization, intercalated disc, and sarcomere-related pathways. qRT-PCR showed increased expression of fibrosis and fibroblast activation markers, while western blotting demonstrated increased MMP2, TIMP1, and Galectin-3 and reduced cardiac troponin I expression in gorilla myocardium. Conclusion This study provides an integrative molecular pathological characterization of ARVC-like cardiomyopathy in a Western lowland gorilla. Although causality cannot be established from a single individual, the convergence of histopathological, genomic, transcriptional, and protein-level evidence supports an ARVC-like cardiomyopathic process as likely contributor to sudden cardiac death and highlights the value of multilayered diagnostic approaches in great ape cardiovascular disease.