PARP-1 expression and activity in primary human lung cells.

Activation of poly(ADP-ribose) polymerase-1 (PARP-1) in response to DNA damage is an important mechanism to keep homeostasis or to trigger apoptosis. The expression and function of (PARP-1) was studied in primary cells cultured from human lung. Normal human bronchial epithelial cells (NHBEC) and peripheral lung cells (PLC) from lung cancer patients were grown as explant cultures and were followed over a period of 12 weeks.

Paracrine effects of CD34 progenitor cells on angiogenic endothelial sprouting.

Background: Progenitor cells contribute to repair of ischemia-associated disturbances of microcirculations, but detailed mechanisms of paracrine angiogenic activation of endothelium by progenitor cells are unclear. The present study was designed to test whether progenitor cells maintain their activation pattern of cytokine secretion and capillary-like endothelial sprout attraction under conditions of hypoxia induced angiogenic activation.

Methods: CD34 progenitor cells were kept separated together with spheroids of human umbilical vein endothelial cells (HUVEC) sharing a common medium supernatant to generate a paracrine diffusion gradient from CD34 cells to the endothelial cell spheroids.

Evidences for age-related modulation of human hematopoietic progenitor cell proliferation.

In order to identify hints of ageing in circulating hematopoietic stem cells (HSCs), putative senescence markers like the cellular level of carbonyl-modified proteins and senescence associated beta-galactosidase activity were measured. Furthermore, the number of HSCs in the periphery and their proliferative capacity in vitro were analyzed in buffy coats of fifty five individuals: 27 young [age, 19-43 years; mean age 31] and 28 middle-aged individuals [age, 45-66 years; mean age 56]. The effect of humoral factors on cell proliferation in culture was studied by expansion of the cells in the presence of plasma pools from children and elderly donors.

Age dependency of the cariporide-mediated cardio-protection after simulated ischemia in isolated human atrial heart muscles.

Experimental and clinical investigations suggest that blockade of Na(+)/H(+) exchange (NHE) with cariporide provides functional protection during ischemia and reperfusion in mature hearts. The benefit on aged human myocardium is unknown. Therefore, the impact of cardiac aging on cardio-protection by cariporide after prolonged ischemia was studied in isolated myocardium of adult (or=70 years) patients with coronary artery disease.

Depression of progenitor cell function by advanced glycation endproducts (AGEs): potential relevance for impaired angiogenesis in advanced age and diabetes.

Diabetes and ageing induce reduction and dysfunction of vascular progenitor cells. Advanced glycation endproducts (AGEs) accumulate in diabetes and ageing. We investigated the influence of AGEs on function of CD34 progenitor cells.

Comparing the global mRNA expression profile of human atrial and ventricular myocardium with high-density oligonucleotide arrays.

Objectives: The knowledge of chamber-specific gene expression in human atrial and ventricular myocardium is essential for the understanding of myocardial function and the basis for the identification of putative therapeutic targets in the treatment of cardiac arrhythmia and heart failure. In this study the gene expression pattern of human left atrial and ventricular myocardium was analyzed.

Methods: Global mRNA expression patterns with high-density oligonucleotide arrays between left atrial and left ventricular myocardium of 6 patients with heart failure undergoing heart transplantation were compared.

Age-dependent depression in circulating endothelial progenitor cells in patients undergoing coronary artery bypass grafting.

Objectives: The effect of patient age on circulating endothelial progenitor cells (EPCs) and their mobilization during coronary artery bypass grafting (CABG) was assessed.

Background: The EPCs are able to contribute to reparative neovascularization after tissue ischemia. In experimental models, reparative neovascularization is impaired in senescent animals, but the role of EPCs in this impairment, especially in humans, is unknown.

Downregulation of cytoskeletal muscle LIM protein by nitric oxide: impact on cardiac myocyte hypertrophy.

Background: In chronic heart failure, myocardial expression of the inducible isoform of nitric oxide (NO) synthase (NOS2) is enhanced, leading to a sustained production of NO. We postulated that NO modulates expression of genes in cardiac myocytes that may be functionally important in the context of cardiac hypertrophy and failure.

Methods And Results: As revealed by cDNA expression array analyses, the NO donor SNAP, which has been shown previously to inhibit agonist-induced cardiac myocyte hypertrophy, downregulates expression of the cytoskeleton-associated muscle LIM protein (MLP) in endothelin-1 (ET-1)-stimulated neonatal rat cardiac myocytes.

Dysfunction of mitochondrial respiratory chain complex I in human failing myocardium is not due to disturbed mitochondrial gene expression.

Objectives: Activity of mitochondrial respiratory chain complexes with and without mitochondrially encoded subunits was assessed in failing human myocardium together with parameters of mitochondrial gene expression.

Background: Mutations and deletions in mitochondrial genome (mtDNA) sporadically accumulate in the aging myocardium. In experimental heart failure, they are discussed to be a generalized problem resulting in disturbances of mitochondrial gene expression and mitochondrial function.

Apoptotic pathway activation from mitochondria and death receptors without caspase-3 cleavage in failing human myocardium: fragile balance of myocyte survival?

Objectives: Activation of the caspase cascade through the mitochondrial and/or death receptor pathway was investigated in the failing human myocardium, in which the mode and extent of the cascade activation are unknown.

Background: In terminal heart failure, a loss of cardiomyocytes by overload-induced apoptosis is an attractive mechanism, explaining the progressive character of the disease. However, its relevance is unclear, because the specificity of probes for apoptotic deoxyribonucleic acid damage is under debate.