Inducible cardiac-specific overexpression of cyclooxygenase-2 (COX-2) confers resistance to ischemia/reperfusion injury.

The role of cyclooxygenase-2 (COX-2) in cardiovascular biology remains controversial. Although COX-2 has been reported to mediate the protective actions of late preconditioning, other studies show that it is also an important mediator of inflammation, toxic shock, and apoptosis, resulting in significant dysfunction and injury in several tissues. To determine whether increased myocardial COX-2, in itself, is protective, cardiac-specific, inducible (Tet-off) COX-2 transgenic (iCOX-2 TG) mice were generated by crossbreeding α-MyHC-tTA transgenic mice (tetracycline transactivator [tTA]) with CMV/TRE-COX-2 transgenic mice.

Myocardial Reparative Properties of Cardiac Mesenchymal Cells Isolated on the Basis of Adherence.

Background: The authors previously reported that the c-kit-positive (c-kit) cells isolated from slowly adhering (SA) but not from rapidly adhering (RA) fractions of cardiac mesenchymal cells (CMCs) are effective in preserving left ventricular (LV) function after myocardial infarction (MI).

Objectives: This study evaluated whether adherence to plastic alone, without c-kit sorting, was sufficient to isolate reparative CMCs.

Methods: RA and SA CMCs were isolated from mouse hearts, expanded in vitro, characterized, and evaluated for therapeutic efficacy in mice subjected to MI.

Repeated doses of cardiac mesenchymal cells are therapeutically superior to a single dose in mice with old myocardial infarction.

We have recently demonstrated that repeated administrations of c-kit cardiac progenitor cells (CPCs) have cumulative beneficial effects in rats with old myocardial infarction (MI), resulting in markedly greater improvement in left ventricular (LV) function compared with a single administration. To determine whether this paradigm applies to other species and cell types, mice with a 3-week-old MI received one or three doses of cardiac mesenchymal cells (CMCs), a novel cell type that we have recently described. CMCs or vehicle were infused percutaneously into the LV cavity, 14 days apart.

Preconditioning Human Cardiac Stem Cells with an HO-1 Inducer Exerts Beneficial Effects After Cell Transplantation in the Infarcted Murine Heart.

The regenerative potential of c-kit(+) cardiac stem cells (CSCs) is severely limited by the poor survival of cells after transplantation in the infarcted heart. We have previously demonstrated that preconditioning human CSCs (hCSCs) with the heme oxygenase-1 inducer, cobalt protoporphyrin (CoPP), has significant cytoprotective effects in vitro. Here, we examined whether preconditioning hCSCs with CoPP enhances CSC survival and improves cardiac function after transplantation in a model of myocardial infarction induced by a 45-minute coronary occlusion and 35-day reperfusion in immunodeficient mice.

c-kit+ Cardiac stem cells alleviate post-myocardial infarction left ventricular dysfunction despite poor engraftment and negligible retention in the recipient heart.

Although transplantation of c-kit+ cardiac stem cells (CSCs) has been shown to alleviate left ventricular (LV) dysfunction induced by myocardial infarction (MI), the number of exogenous CSCs remaining in the recipient heart following transplantation and their mechanism of action remain unclear. We have previously developed a highly sensitive and accurate method to quantify the absolute number of male murine CSCs in female recipient organs after transplantation. In the present study, we used this method to monitor the number of donor CSCs in the recipient heart after intracoronary infusion.

The COX-2/PGI2 receptor axis plays an obligatory role in mediating the cardioprotection conferred by the late phase of ischemic preconditioning.

Background: Pharmacologic studies with cyclooxygenase-2 (COX-2) inhibitors suggest that the late phase of ischemic preconditioning (PC) is mediated by COX-2. However, nonspecific effects of COX-2 inhibitors cannot be ruled out, and the selectivity of these inhibitors for COX-2 vs. COX-1 is only relative.