6 research outputs found
The effect of bone marrow microenvironment on the functional properties of the therapeutic bone marrow-derived cells in patients with acute myocardial infarction
<p>Abstract</p> <p>Background</p> <p>Treatment of acute myocardial infarction with stem cell transplantation has achieved beneficial effects in many clinical trials. The bone marrow microenvironment of ST-elevation myocardial infarction (STEMI) patients has never been studied even though myocardial infarction is known to cause an imbalance in the acid-base status of these patients. The aim of this study was to assess if the blood gas levels in the bone marrow of STEMI patients affect the characteristics of the bone marrow cells (BMCs) and, furthermore, do they influence the change in cardiac function after autologous BMC transplantation. The arterial, venous and bone marrow blood gas concentrations were also compared.</p> <p>Methods</p> <p>Blood gas analysis of the bone marrow aspirate and peripheral blood was performed for 27 STEMI patients receiving autologous stem cell therapy after percutaneous coronary intervention. Cells from the bone marrow aspirate were further cultured and the bone marrow mesenchymal stem cell (MSC) proliferation rate was determined by MTT assay and the MSC osteogenic differentiation capacity by alkaline phosphatase (ALP) activity assay. All the patients underwent a 2D-echocardiography at baseline and 4 months after STEMI.</p> <p>Results</p> <p>As expected, the levels of pO<sub>2</sub>, pCO<sub>2</sub>, base excess and HCO<sub>3 </sub>were similar in venous blood and bone marrow. Surprisingly, bone marrow showed significantly lower pH and Na<sup>+ </sup>and elevated K<sup>+ </sup>levels compared to arterial and venous blood. There was a positive correlation between the bone marrow pCO<sub>2 </sub>and HCO<sub>3 </sub>levels and MSC osteogenic differentiation capacity. In contrast, bone marrow pCO<sub>2 </sub>and HCO<sub>3 </sub>levels displayed a negative correlation with the proliferation rate of MSCs. Patients with the HCO<sub>3 </sub>level below the median value exhibited a more marked change in LVEF after BMC treatment than patients with HCO<sub>3 </sub>level above the median (11.13 ± 8.07% vs. 2.67 ± 11.89%, P = 0.014).</p> <p>Conclusions</p> <p>Low bone marrow pCO<sub>2 </sub>and HCO<sub>3 </sub>levels may represent the optimal environment for BMCs in terms of their efficacy in autologous stem cell therapy in STEMI patients.</p
Paraoxonase Polymorphism and CAD Rapid Publication The Gln-Arg191 Polymorphism of the Human Paraoxonase Gene (HUMPONA) Is Not Associated with the Risk of Coronary Artery Disease in Finns
A novel functional polymorphism in the PECAM-1 gene (53G>A) is associated with progression of atherosclerosis in the LOCAT and REGRESS studies
A 53G>A polymorphism identified in the 5' untranslated region (5'UTR) of the platelet endothelial cell adhesion molecule-1 (PECAM-1) gene alters a putative shear stress responsive element (SSRE). PECAM-1 was shown to be responsive to shear stress and transient transfection of human umbilical vein endothelial cell (HUVECs) with two luciferase reporter constructs driven by the PECAM-1 promoter and 5'UTR showed a response of the 53G allele, not the 53A allele, to shear stress. Association between the 53G>A, and the previously published L125V polymorphism, and coronary atherosclerosis was examined in two angiographic studies. The frequencies of the rare alleles of the 53G>A and L125V polymorphisms were 0.01 and 0.49, respectively, in the Lopid Coronary Angiography Trial (LOCAT) study and 0.02 and 0.49, respectively, in the Regression Growth Evaluation Statin Study (REGRESS) study. Compared with 53G homozygotes, carriers of the 53A allele showed less focal progression of disease in the LOCAT study and a similar trend in the diffuse progression of disease in the REGRESS study, whereas no association between L125V and coronary atherosclerosis was observed in either study. These data demonstrate that the PECAM-1 gene is responsive to shear stress in vitro and that decreased PECAM-1 gene expression in 53A carriers may influence reduced progression of vessel stenosis in patients with coronary artery diseas