Lncrna-ptpre in cardiac dysfunction - management of cardiac dysfunction and heart failure remains a major challenge in ischemic heart disease

The National Heart, Lung, and Blood Institute awarded New York Institute of Technology $573,750 on July 15, 2026, to investigate the role of long noncoding RNA PTPRE (lncRNA-PTPRE) in cardiac dysfunction and heart failure under the Cardiovascular Diseases Research program (CFDA 93.837).

The research examines how lncRNA-PTPRE mediates thyroid hormone-dependent cardioprotection, building on preliminary findings that expression of this lncRNA is impaired in hypothyroid mouse hearts and in hearts with infarction-driven cardiac dysfunction. The work will characterize molecular, functional, and pathophysiological connections between cardiac lncRNAs and the thyroid hormone pathway, with attention to potential anti-inflammatory mechanisms. The project runs through June 30, 2029, with performance at 2400 E Highland Drive, Suite 300, Jonesboro, Arkansas.

This is a project grant, the standard assistance type under NHLBI's cardiovascular research portfolio. NYIT, a private nonprofit educational institution, serves as the recipient organization.

A majority of the ~98% of the human genome, consisting of non-protein-coding DNA sequences, codes for long noncoding rnas (lncrnas; transcripts >200 nucleotides). The majority of disease- and trait-associated variants emerging from genome-wide association studies were reported to LIE within the noncoding regions. In addition, over 90% of the genome is transcribable, and noncoding rnas offer enormous diagnostic and therapeutic potential. Lncrna genes outnumber protein-coding genes by multiple folds in mice and humans, yet only a small fraction of transcripts have been characterized, especially in the heart. Low thyroid hormone (TH) function (hypothyroidism; hypoth) is a major cardiovascular risk factor. However, correction of systemic hypoth may not improve cardiac tissue hypoth or cardiac function. Thus, novel heart-specific targets in the TH pathway are warranted. Deiodinase type 3 catalyzes the conversion of active forms of THS into their inactive metabolites, and lncrnas have been identified in the enzyme's chromosomal domain. We recently showed the involvement of lncrnas in caloric restriction-mediated cardiac atrophy with TH dysfunction. We also showed that lncrnas interact with mirnas and mrnas in TH-mediated improvement in cardiac function. However, the specific molecular, functional, and pathophysiological connections between cardiac lncrnas and the TH pathway are unclear. Early studies from our laboratory show that expression of lncrna-ptpre (human ortholog) is significantly impaired in primary hypothyroid mouse hearts and also in the hearts of infarction-driven cardiac dysfunction associated with hypoth. TH supplementation reversed their expression levels. Data also indicate potential anti-inflammatory roles for this lncrna in the heart. We hypothesize that lncrna-ptpre is cardioprotective and is mediated by THS. Aim-1 will investigate the extent to which THS regulate lncrna-ptpre in cardiac cells in vitro. We will study this in both primary isolated adult mouse cardiomyocytes and primary cardiac fibroblasts and investigate the underlying mechanisms. We will employ small interfering RNA and gene overexpression methods via a nano-magnetofection strategy. Aim-2 will determine the molecular and pathophysiological significance of activation of lncrna-ptpre in vivo using a clinically relevant model of high- FAT diet-induced occlusive coronary infarction and cardiac dysfunction associated with hypoth. We will accomplish these using crispra-based gene activation technology via viral vector approaches. We will also employ a first-in-the-world, custom-designed nanoindentation technology to study cardiac mechanical effects. These studies will serve as the first major step in the identification of novel roles of lncrna-ptpre in the cardiac-thyroid axis, offering potential human clinical translational opportunities.