LncRNA Mediated Mitophagy in Cardioprotection
Description: This Bridge Transformational Project will define the physiological and mechanistic role of the cardiac long noncoding RNA Camirt in maintaining mitochondrial integrity during myocardial injury, aging, and the transition to heart failure, while directly addressing prior NIH reviewer concerns regarding Cre-related cardiotoxicity. To eliminate confounding effects associated with constitutive aMHC-Cre expression, we will employ rigorously validated tamoxifen-inducible, cardiac-specific Camirt loss- and gain-of-function mouse models (Camirt-icKO and Camirt-icKI) using aMHC-MerCreMer. We will perform longitudinal assessments of cardiac structure, function, and survival, complemented by invasive hemodynamic measurements, histopathology, biomarker analysis, and ultrastructural evaluation of mitochondrial health. Transcriptomic profiling will identify Camirt-dependent pathways governing mitophagy, mitochondrial dynamics, oxidative stress, fibrosis, and hypertrophy. Finally, mechanistic studies using the mt-Keima mitophagy biosensor will define how Camirt–PHB2 signaling regulates mitochondrial quality control in cardiomyocytes across the lifespan and under oxidative stress. Together, these studies will generate definitive, high-impact preclinical evidence establishing Camirt as a key regulator of mitochondrial homeostasis in the heart and provide a strong, risk-mitigated foundation for a competitive NIH R01 application targeting Camirt-mediated mitophagy as a therapeutic strategy for heart failure.
Funder: American Heart Association
Amount: $99,990
Funding type: research
Funder scheme: Bridge Transformational Project Award
Start date: 2026-04-01
End date: 2027-03-31
Investigators: Chuanxi Cai, Chuanxi Cai
Institution: University of Virginia
Funded outputs count: 0
Funder award ID: 26BTPA1622778
OpenAlex ID: G7396049700