Generation of inducible mitophagy mice.

Mitophagy is programmed selective autophagy of mitochondria and is important for mitochondrial quality control and cellular homeostasis. Mitochondrial dysfunction and impaired mitophagy are closely associated with various diseases, including heart failure and diabetes. To better understand the pathophysiological role of mitophagy, we generated doxycycline-inducible mitophagy mice using a synthetic mitophagy adaptor protein consisting of an outer mitochondrial membrane targeting sequence and an engineered LIR. To evaluate the activation of mitophagy upon doxycycline treatment, we also generated mitophagy reporter mito-QC mice in which mitochondria tandemly express mCherry and GFP, and only GFP signals are lost in acidic lysosomes subjected to mitophagy. With the ROSA26 promoter-driven rtTA, mitophagy was observed at least in heart, liver, and skeletal muscle. We investigated the relationship between mitophagy activation and pressure overload heart failure or high fat diet-induced obesity. Unexpectedly, we were unable to confirm the protective effect of mitophagy in these two pathological models. Further titration of the level of mitophagy induction is required to demonstrate the potency of the protective effects of mitophagy in disease models.

Late onset of coronary ostial stenosis following surgical aortic valve replacement in a patient with anomalous origin of the right coronary artery.

Surgical aortic valve replacement (SAVR) in patients with anomalous origination of a coronary artery from the opposite sinus is associated with risk for myocardial ischemia during the perioperative period. [1] However, iatrogenic coronary ostial stenosis (ICOS) generally occurs within the first 6 months after SAVR. We present an unusual case of a 74-year-old man with anomalous origination of the right coronary artery from the left coronary sinus, who developed effort angina due to ICOS 19 months following SAVR and ascending aorta replacement. Angiography and computed tomography were utilized to perform a comparison before and after the procedure. From the results, it was evident that the flattened mild stenosis preoperatively was caused by anomalous origination of a coronary artery from the opposite sinus and progressed to severe stenosis by ICOS after the procedure. The patient was successfully treated with percutaneous coronary intervention. .