The cardiovascular system ensures the delivery of oxygen and nutrients to all cells, tissues, and organs. Under extended exposure to reduced oxygen levels, cells are able to survive through the transcriptional activation of a series of genes that participate in angiogenesis, glucose metabolism, and cell proliferation. The oxygen-sensitive transcriptional activator HIF-1 (hypoxia-inducible factor-1) is a key transcriptional mediator of the response to hypoxic conditions. The HIF-1 pathway was found to be a master regulator of angiogenesis. Whether the process is physiological or pathological, HIF-1 seems to participate in vasculature formation by synergistic correlations with other proangiogenic factors such as VEGF (vascular endothelial growth factor), PlGF (placental growth factor), or angiopoietins. Considering the important contributions of HIF-1 in angiogenesis and vasculogenesis, it should be considered a promising target for treating ischaemic diseases or cancer. In this review, we discuss the roles of HIF-1 in both physiological/pathophysiological angiogenesis and potential strategies for clinical therapy.

There is a dynamic interplay between pro- and anti-oxidant substances in human ejaculate. Excessive reactive oxygen species (ROS) generation can overwhelm protective mechanism and initiate changes in lipid and/or protein layers of sperm plasma membranes. Additionally, changes in DNA can be induced. The essential steps of lipid peroxidation have been listed as well as antioxidant substances of semen. A variety of detection techniques of lipid peroxidation have been summarized together with the lipid components of sperm membranes that can be subjected to stress. It is unsolved, a threshold for ROS levels that may induce functional sperm ability or may lead to male infertility.

The genetic basis of nonobstructive azoospermia is unknown in the majority of infertile men. We performed array comparative genomic hybridization testing in blood samples obtained from 15 patients with azoospermia, and we performed mutation screening by means of direct Sanger sequencing of the testis-expressed 11 gene (TEX11) open reading frame in blood and semen samples obtained from 289 patients with azoospermia and 384 controls. We identified a 99-kb hemizygous loss on chromosome Xq13.2 that involved three TEX11 exons. This loss, which was identical in 2 patients with azoospermia, predicts a deletion of 79 amino acids within the meiosis-specific sporulation domain SPO22. Our subsequent mutation screening showed five novel TEX11 mutations: three splicing mutations and two missense mutations. These mutations, which occurred in 7 of 289 men with azoospermia (2.4%), were absent in 384 controls with normal sperm concentrations (P=0.003). Notably, five of those TEX11 mutations were detected in 33 patients (15%) with azoospermia who received a diagnosis of azoospermia with meiotic arrest. Meiotic arrest in these patients resembled the phenotype of Tex11-deficient male mice. Immunohistochemical analysis showed specific cytoplasmic TEX11 expression in late spermatocytes, as well as in round and elongated spermatids, in normal human testes. In contrast, testes of patients who had azoospermia with TEX11 mutations had meiotic arrest and lacked TEX11 expression. In our study, hemizygous TEX11 mutations were a common cause of meiotic arrest and azoospermia in infertile men. (Funded by the National Institutes of Health and others.)

Aims Several experimental studies and the initial clinical experience have shown that autologous skeletal myoblast transplantation into the area of post-infarction left ventricular injury results in an increase in segmental contractile performance. This phase I clinical trial was designed to assess the feasibility and safety of autologous skeletal myoblast transplantation performed via a percutaneous trans-coronary-venous approach in patients with post-infarction left ventricular dysfunction. Methods and results Ten patients with heart failure and presence of an akinetic or a dyskinetic post-infarction injury with no viable myocardium were included in the study. Skeletal myoblasts were obtained from a biopsy specimen and grown in cell culture. Patients were treated with prophylactic amiodarone infusion before and during the procedure, except one patient. Skeletal myoblast transplantations were performed uneventfully in nine patients using the TransAccess^® catheter system under fluoroscopic and intravascular ultrasound guidance. In one patient, the procedure was not performed because of the inability of appropriate coronary sinus guiding wire positioning across venous valve. In five patients, the anterior interventricular vein and in four patients, the middle cardiac vein were used to access the myocardium. Two to four intramyocardial injections 1.5–4.5 cm deep were performed in each patient, delivering up to 100 million cells in 0.4–2.5 mL of saline. During 6 months follow-up, New York Heart Association class improved in all patients and ejection fraction increased 3–8% in six out of nine cases. Conclusion These data suggest the feasibility and procedural safety of myoblast transplantation performed via the trans-coronary-venous approach using the TransAccess catheter system.