Novel approaches to determine the functional role of cardiomyocyte specific E3 ligase, Pellino-1 following myocardial infarction.

Objectives: Ubiquitination plays a vital role in controlling vascular inflammation, cellular protein quality control, and minimizing misfolded protein toxicity. Pellino-1 (Peli1), a type of E3 ubiquitin ligase, has emerged as a critical regulator of the innate immune response; however, its role in the repair and regeneration of ischemic myocardium remains to be elucidated.

Methods: Mice (8-12 weeks old, male and females) were divided into (i) Wild type (ii) cardiomyocyte-specific Peli1 overexpressed (AMPEL1), (iii) cardiomyocyte-specific Peli1 knockout (CP1KO) and were subjected to sham and left anterior descending artery ligation.

Role of Pellino-1 in Inflammation and Cardioprotection following Severe Sepsis: A Novel Mechanism in a Murine Severe Sepsis Model .

Objectives: Intra-abdominal sepsis is commonly diagnosed in the surgical population and remains the second most common cause of sepsis overall. Sepsis-related mortality remains a significant burden in the intensive care unit despite advances in critical care. Nearly a quarter of the deaths in people with heart failure are caused by sepsis.

Protective Effect of Cardiomyocyte-Specific Prolyl-4-Hydroxylase 2 Inhibition on Ischemic Injury in a Mouse MI Model.

Background: Our earlier studies showed that inhibiting prolyl-4-hydroxylase enzymes (PHD-1 and PHD-3) improves angiogenesis, heart function, and limb perfusion in mouse models via stabilizing hypoxia-inducible transcription factor-alpha (HIF-1α). The present study explored the effects of the prolyl-4-hydroxylase enzyme, PHD-2, on ischemic heart failure using cardiac-specific PHD-2 gene knockout (KO) mice (PHD2 -/- ).

Study Design: Adult wild-type (WT) and PHD2 -/- mice, 8-12 weeks old, were subjected to myocardial infarction (MI) by irreversibly ligating the left anterior descending (LAD) coronary artery.

Gene therapy with Pellino-1 improves perfusion and decreases tissue loss in Flk-1 heterozygous mice but fails in MAPKAP Kinase-2 knockout murine hind limb ischemia model.

Objectives: In the United States, over 8.5 million people suffer from peripheral arterial disease (PAD). Previously we reported that Pellino-1(Peli1) gene therapy reduces ischemic damage in the myocardium and skin flaps in Flk-1 [Fetal Liver kinase receptor-1 (Flk-1)/ Vascular endothelial growth factor receptor-2/VEGFR2] heterozygous (Flk-1) mice.