Wisp2 super-enhancer–associated RNA (Wisper)

Wisper (Wisp2 super-enhancer–associated RNA) is a cardiac fibroblast-enriched long non-coding RNA transcribed from a cardiac-specific super-enhancer region. It is highly upregulated following myocardial infarction or pressure overload and plays a central role in regulating the proliferation, migration, survival, and gene expression profile of cardiac fibroblasts. Functionally, it controls extracellular matrix deposition by modulating key profibrotic factors such as collagen genes (Col3a1), fibronectin (Fn1), TGF-beta 2 (Tgfb2), and influences alternative splicing events through interaction with TIA1-related protein—particularly affecting lysyl hydroxylase 2 (Plod2/LH2), which is involved in collagen cross-linking. In both mouse models and human patients with heart disease or aortic stenosis, increased Wisper levels correlate with the extent and severity of fibrosis. Therapeutically targeting Wisper using antisense oligonucleotides has been shown to reduce established fibrosis after injury without affecting other organs like the kidney; however, pre-injury knockdown can compromise necessary wound healing responses. These findings position Wisper as an attractive therapeutic target for reducing pathological cardiac fibrosis while highlighting potential safety considerations regarding timing and context for intervention.

Other names

WisperWisp2 super-enhancer-associated RNAlncRNA Wisper

Inhibition by antisense oligonucleotides leads to reduced expression of profibrotic genes, decreased collagen production, and attenuation of pathological fibrosis