fibrin and Hypertrophy--Left-Ventricular

The mechanism by which endogenous progenitor cells contribute to functional and beneficial effects in stem cell therapy remains unknown.. Utilizing a novel (31)P magnetic resonance spectroscopy-2-dimensional chemical shift imaging method, this study examined the heterogeneity and bioenergetic consequences of postinfarction left ventricular (LV) remodeling and the mechanisms of endogenous progenitor cell contribution to the cellular therapy.. Human embryonic stem cell-derived vascular cells (hESC-VCs) that stably express green fluorescent protein and firefly luciferase (GFP(+)/Luc(+)) were used for the transplantation. hESC-VCs may release various cytokines to promote angiogenesis, prosurvival, and antiapoptotic effects. Both in vitro and in vivo experiments demonstrated that hESC-VCs effectively inhibit myocyte apoptosis. In the mouse model, a fibrin patch-based cell delivery resulted in a significantly better cell engraftment rate that was accompanied by a better ejection fraction. In the swine model of ischemia-reperfusion, the patch-enhanced delivery of hESC-VCs resulted in alleviation of abnormalities including border zone myocardial perfusion, contractile dysfunction, and LV wall stress. These results were also accompanied by a pronounced recruitment of endogenous c-kit(+) cells to the injury site. These improvements were directly associated with a remarkable improvement in myocardial energetics, as measured by a novel in vivo (31)P magnetic resonance spectroscopy-2-dimensional chemical shift imaging technology.. The findings of this study demonstrate that a severely abnormal heterogeneity of myocardial bioenergetics in hearts with postinfarction LV remodeling can be alleviated by the hESC-VCs therapy. These findings suggest an important therapeutic target of peri-scar border zone and a promising therapeutic potential for using hESC-VCs together with the fibrin patch-based delivery system.

Topics: Adenosine Triphosphate; Animals; Apoptosis; Cell Line; Cell Movement; Cell Tracking; Coronary Circulation; Disease Models, Animal; Embryonic Stem Cells; Endothelial Cells; Energy Metabolism; Female; Fibrin; Green Fluorescent Proteins; Humans; Hypertrophy, Left Ventricular; Luciferases, Firefly; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred NOD; Mice, SCID; Myocardial Contraction; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Myocytes, Smooth Muscle; Phosphocreatine; Proto-Oncogene Proteins c-kit; Recovery of Function; Stem Cell Transplantation; Stroke Volume; Swine; Time Factors; Tissue Scaffolds; Transfection; Ventricular Function, Left; Ventricular Remodeling

The relationship among daily cigarette consumption, washed and non-washed RBC filterability time (FT) as an indicator of erythrocyte deformability and echocardiographic left ventricular mass (LVM) were examined in 25 clinically healthy smokers and in 25 non-smoking controls matched for sex and age. FT of non-washed RBC was significantly higher in smokers than in non-smokers (25.2 +/- 3.6 vs. 16.8 +/- 2.2 min, P < 0.001). A highly significant linear correlation between number of cigarette consumption and FT was found. These differences were not observed when RBC were washed three times with isotonic saline. LVM was significantly greater in smokers (85.5 +/- 13.4 g/m2) than in controls (61.8 +/- 6.7 g/m2, P < 0.001). A linear correlation between daily cigarette consumption and LVM was observed. A positive relationship between LVM and FT of non-washed RBC was also found. These results demonstrated that LVM is significantly elevated in smokers and is linearly correlated with both cigarette consumption and RBC filtratibility. The increased deformability found in smokers may be a determinant to the cardiac hypertrophy. The association of both elevated LVM and rheological impairment may indicate unfavourable prognosis.

Topics: Adult; Echocardiography; Erythrocyte Deformability; Female; Fibrin; Hematocrit; Humans; Hypertrophy, Left Ventricular; Leukocyte Count; Male; Middle Aged; Risk Factors; Smoking