Phosphodiesterase 9a Inhibition in Mouse Models of Diastolic Dysfunction.

Background: Low myocardial cGMP-PKG (cyclic guanosine monophosphate-protein kinase G) activity has been associated with increased cardiomyocyte diastolic stiffness in heart failure with preserved ejection fraction. Cyclic guanosine monophosphate is mainly hydrolyzed by PDE (phosphodiesterases) 5a and 9a. Importantly, PDE9a expression has been reported to be upregulated in human heart failure with preserved ejection fraction myocardium and chronic administration of a PDE9a inhibitor reverses preestablished cardiac hypertrophy and systolic dysfunction in mice subjected to transverse aortic constriction (TAC).

Remodeling Failing Human Myocardium With Hybrid Cell/Matrix and Transmyocardial Revascularization.

Given the limited treatment options for advanced heart failure, the intrinsic regenerative properties of stem cells have been evaluated for myocardial remodeling. Previous stem cells techniques for myocardiocyte remodeling have been limited by the low cellular retention. Presented is a hybrid approach for remodeling infarcted myocardium through implantation of allogeneic human amniotic fluid-derived mesenchymal stem cells within micronized human allograft-derived liquid matrix during the performance of transmyocardial revascularization (TMR).

Cardiac Regeneration in the Human Left Ventricle After CorMatrix Implantation.

CorMatrix is an organic extracellular matrix (ECM) derived from porcine small intestine submucosa and is used for pericardial closure and cardiac tissue repair. During explantation of a HeartMate II (Thoratec Corp, Pleasanton, CA) left ventricular assist device (LVAD) because of infection, CorMatrix was used to repair the left ventricular apex and aorta. Three months later, a HeartWare HVAD (HeartWare International, Inc, Framingham, MA) was implanted for recurrent heart failure.

Improved metabolism and redox state with a novel preservation solution: implications for donor lungs after cardiac death (DCD).

Lungs donated after cardiac death (DCD) are an underutilized resource for a dwindling donor lung transplant pool. Our study investigates the potential of a novel preservation solution, Somah, to better preserve statically stored DCD lungs, for an extended time period, when compared to low-potassium dextran solution (LPD). We hypothesize that Somah is a metabolically superior organ preservation solution for hypothermic statically stored porcine DCD lungs, possibly improving lung transplant outcomes.

Adipose-derived human stem/stromal cells: comparative organ specific mitochondrial bioenergy profiles.

Background: Adipose-derived stem/stromal cells (ASCs) isolated from the stromal vascular fraction are a source of mesenchymal stem cells that have been shown to be beneficial in many regenerative medicine applications. ASCs are an attractive source of stem cells in particular, due to their lack of immunogenicity. This study examines differences between mitochondrial bioenergetic profiles of ASCs isolated from adipose tissue of five peri-organ regions: pericardial, thymic, knee, shoulder, and abdomen.

Endosomal regulation of contact inhibition through the AMOT:YAP pathway.

Contact-mediated inhibition of cell proliferation is an essential part of organ growth control; the transcription coactivator Yes-associated protein (YAP) plays a pivotal role in this process. In addition to phosphorylation-dependent regulation of YAP, the integral membrane protein angiomotin (AMOT) and AMOT family members control YAP through direct binding. Here we report that regulation of YAP activity occurs at the endosomal membrane through a dynamic interaction of AMOT with an endosomal integral membrane protein, endotubin (EDTB).

Differential growth and multicellular villi direct proepicardial translocation to the developing mouse heart.

In the mammalian system the proepicardium (PE) arises from mesothelium of the septum transversum before translocation to the heart where it forms the epicardium and progenitor cells of the coronary vessels. Despite its importance, the process in which PE cells translocate to the myocardium in mammals is not well defined. The current paradigm states that cellular cysts of PE float across the pericardial space and contact the outer surface of the myocardium.