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Description
Cardiovascular disease is the leading cause of death worldwide, being ischemic heart disease and endomyocardial fibrosis the primary reasons of end-stage heart failure (HF). Cardiac fibrosis is the pathological process mediated by cardiac fibroblasts (cFbs) and determined by the maladaptive remodelling of the heart extracellular matrix (ECM). Although it underlies most of cardiac disfunctions, effective therapies for its inhibition or reversion are currently not available. Long non-coding RNAs (lncRNAs) are potent transcriptional regulators which might be involved in the cardiac fibrotic process and - therefore - have emerged as viable prognosis makers and therapeutical targets. To investigate the role of lncRNAs during fibrotic progression, we differentiated induced pluripotent stem cells (hiPSCs) into cFbs (hiPSC-cFbs) and exposed them to a TGFb-induced fibrotic assay. Following the fibrotic trigger, a subset of fibrosis-related lncRNAs was found dysregulated. A similar trend was observed in primary cultures of cFbs derived from HF patients as compared to the same cells obtained from healthy donors. To better model cardiac fibrosis progression, iPS-cFbs were co-cultured with isogenic hiPSCs-derived cardiomyocytes (iPS-CMs) to generate patient-specific three-dimensional cardiac organoids. This model will be further exploited to test the role of individual lncRNAs by altering their expression through GapmeRs.
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