TCONS_00052110 is associated with prolonged PTBP1 half-life and mitochondrial injury in PAH-associated right ventricular stress.

Right ventricular failure (RVF) is the major cause of mortality in pulmonary arterial hypertension (PAH), and even mild inflammatory stress can precipitate rapid decompensation. Here we report that the long noncoding RNA TCONS_00052110 (TCONS) is upregulated in the right ventricle (RV) under inflammatory stress and may modulate stress-associated responses. In adult male Sprague-Dawley rats with monocrotaline-induced PAH, a low-dose lipopolysaccharide challenge precipitated acute RVF. Mechanistically, TCONS physically associates with polypyrimidine tract-binding protein 1 (PTBP1) and is associated with a prolonged PTBP1 protein half-life, consistent with reduced PTBP1 protein turnover. Elevated PTBP1 skews pyruvate kinase muscle (PKM) isoforms toward PKM2, favoring a PKM2-dominant metabolic state consistent with glycolysis-related remodeling. These changes are accompanied by mitochondrial injury and cytosolic cytochrome c release in vivo and in vitro. Using a cardiomyocyte-enriched AAV9-cTnT strategy, knockdown of TCONS was associated with normalization of the PKM2/PKM1 balance, attenuation of mitochondrial injury, preservation of RV functional indices after inflammatory challenge, and improved survival. Reanalysis of patient-derived datasets from PAH lung tissue and RV tissue spanning compensation-to-decompensation revealed enrichment of inflammatory and glycolysis-related pathways concordant with the TCONS-PTBP1 axis, supporting contextual relevance. These findings support a model of a post-transcriptional link between inflammatory stress, glycolysis-related remodeling, and mitochondrial injury in PAH-related RVF, warranting validation in human RV tissue.