Critical Role for Leukocyte Hypoxia Inducible Factor-1α Expression in Post-Myocardial Infarction Left Ventricular Remodeling

Abstract

The remodeling process can cause myocardial rupture, lead to LV dilation and ultimately cause decreased functional reserve and congestive heart failure. 1 We have previously suggested that inflammation plays a critical role in post-MI LV remodeling 2 but not infarct size. Increased WBC count is linked to increased LV size in patients with MI 3,4 and inflammation most likely associates with unfavorable outcomes by increasing the infarct size or altering ventricular remodeling. 5 Direct inhibition of WBC infiltration through the administration of an antibody to CD11b failed to reduce infarct size; however, inhibition of WBC infiltration remains a potential target to optimizing cardiac remodeling post-MI.Chemokines play an important role in the myocardial healing after MI. 6,7 Earlier data demonstrated that blocking CC chemokines is helpful in the prevention of post ischemic Original

Early upregulation of myocardial CXCR4 expression is critical for dimethyloxalylglycine-induced cardiac improvement in acute myocardial infarction

“…Myocardial infarction was induced in mice as described (8). Briefly, animals were anesthetized with xylazine/ketamine combination (ip injection, ketamine 75 Mg/kg; xylazine 7.5 Mg/kg; about 0.07 ml for 30-g mouse).…”

“…Two-dimension echocardiography was performed with a 15-MHz linear array transducer interfaced with a Sequoia C256 (Acuson) as preciously described (8). Briefly, baseline before LAD ligation as well as 3 and 21 d after LAD ligation, left ventricle (LV) dimensions were quantified by digitally recorded 2D clips and M-mode images from the mid-LV just below the papillary muscles to allow for consistent measurements from the same anatomical location in different mice.…”

Lentiviral vectors and cardiovascular diseases: a genetic tool for manipulating cardiomyocyte differentiation and function

“…[35][36][37][38][39] For example, LVV-mediated prodynorphin overexpression in mouse stem cells induces a remarkable enhancement of the expression of the two cardiac-promoting genes GATA-4 and Nkx2.5, resulting in a dramatic increase of spontaneous beating activity. 38 In another study, Koyanagi et al 37 provided evidence that Sox2 enhances the pluripotency of circulating mesangioblasts and facilitates their differentiation towards the cardiac lineage; in addition, a significant improvement of cardiac function was observed in vivo after transplantation of the Sox2-transduced cells in mice models of myocardial infarction.…”

“…In fact, LLVs are being increasingly tested for applications in preclinical studies. [34][35][36][37]39,[64][65][66] LVVs have also been used successfully for reprogramming strategies that generate iPS cells and for the transdifferentiation of somatic cells. However, safety issue concerns are still restraining their use in the clinical setting: indeed, LVVs do have the potential drawback of causing insertional mutagenesis through the random integration of DNA into the host genome, leading to the aberrant expression of important genes and to tumorigenesis.…”

Stem Cell Therapy in Myocardial Infarction Clinical Point of View and the Results of the REANIMA Study (REgenerAtion of Myocardium with boNe Marrow Mononuclear Cells in MyocArdial Infarction)

“…The most important steps are shown in figure one. Ischemic injury induces the hypoxia-inducible factor-alpha which in turns stimulates the expression of several growth factors and chemokines in the infracted heart (Dong et al, 2010). Those cytokines, especially stromal derived factor-1, interleukin-8 and vascular-endothelial growth factor promote mobilization of local and remote stem cells and enable engraftment of them into the damaged tissue ( Figure 1).…”