Mitochondrial dynamics and cell death in heart failure.

The highly regulated processes of mitochondrial fusion (joining), fission (division) and trafficking, collectively called mitochondrial dynamics, determine cell-type specific morphology, intracellular distribution and activity of these critical organelles. Mitochondria are critical for cardiac function, while their structural and functional abnormalities contribute to several common cardiovascular diseases, including heart failure (HF). The tightly balanced mitochondrial fusion and fission determine number, morphology and activity of these multifunctional organelles.

Mitochondrial DNA maintenance: an appraisal.

Mitochondria play a crucial role in a variety of cellular processes ranging from energy metabolism, generation of reactive oxygen species (ROS), and Ca(2+) handling to stress responses, cell survival, and death. Malfunction of the organelle may contribute to the pathogenesis of neuromuscular disorders, cancer, premature aging, and cardiovascular diseases, including myocardial ischemia, cardiomyopathy, and heart failure. Mitochondria are unique as they contain their own genome organized into DNA-protein complexes, so-called mitochondrial nucleoids, along with multiprotein machineries, which promote mitochondrial DNA (mtDNA) replication, transcription, and repair.

Epigenetics of the failing heart.

With the impressive advancement in high-throughput 'omics' technologies over the past two decades, epigenetic mechanisms have emerged as the regulatory interface between the genome and environmental factors. These mechanisms include DNA methylation, histone modifications, ATP-dependent chromatin remodeling and RNA-based mechanisms. Their highly interdependent and coordinated action modulates the chromatin structure controlling access of the transcription machinery and thereby regulating expression of target genes.

Mitochondrial oxidative metabolism and uncoupling proteins in the failing heart.

Despite significant progress in cardiovascular medicine, myocardial ischemia and infarction, progressing eventually to the final end point heart failure (HF), remain the leading cause of morbidity and mortality in the USA. HF is a complex syndrome that results from any structural or functional impairment in ventricular filling or blood ejection. Ultimately, the heart's inability to supply the body's tissues with enough blood may lead to death.

Myocardial regeneration of the failing heart.

Human heart failure (HF) is one of the leading causes of morbidity and mortality worldwide. Currently, heart transplantation and implantation of mechanical devices represent the only available treatments for advanced HF. Two alternative strategies have emerged to treat patients with HF.

Mitochondria in heart failure: the emerging role of mitochondrial dynamics.

Over the past decade, mitochondria have emerged as critical integrators of energy production, generation of reactive oxygen species (ROS), multiple cell death, and signaling pathways in the constantly beating heart. Clarification of the molecular mechanisms, underlying mitochondrial ROS generation and ROS-induced cell death pathways, associated with cardiovascular diseases, by itself remains an important aim; more recently, mitochondrial dynamics has emerged as an important active mechanism to maintain normal mitochondria number and morphology, both are necessary to preserve cardiomyocytes integrity. The two opposing processes, division (fission) and fusion, determine the cell type-specific mitochondrial morphology, the intracellular distribution and activity.

Polycyclic aromatic hydrocarbons impair function of β2-adrenergic receptors in airway epithelial and smooth muscle cells.

Incomplete combustion produces a pollutant mixture that includes polycyclic aromatic hydrocarbons (PAHs). Previous work by the Columbia Center for Children's Environmental Health (CCCEH) and others linked exposure to PAH with symptoms of asthma and other adverse health effects in young children. Inhaled β(2)-adrenergic agonists are mainstays in the treatment of reactive airway diseases.

Adenosine regulation of alveolar fluid clearance.

Adenosine is a purine nucleoside that regulates cell function through G protein-coupled receptors that activate or inhibit adenylyl cyclase. Based on the understanding that cAMP regulates alveolar epithelial active Na(+) transport, we hypothesized that adenosine and its receptors have the potential to regulate alveolar ion transport and airspace fluid content. Herein, we report that type 1 (A(1)R), 2a (A(2a)R), 2b (A(2b)R), and 3 (A(3)R) adenosine receptors are present in rat and mouse lungs and alveolar type 1 and 2 epithelial cells (AT1 and AT2).

Interdependency of beta-adrenergic receptors and CFTR in regulation of alveolar active Na+ transport.

Beta-adrenergic receptors (betaAR) regulate active Na+ transport in the alveolar epithelium and accelerate clearance of excess airspace fluid. Accumulating data indicates that the cystic fibrosis transmembrane conductance regulator (CFTR) is important for upregulation of the active ion transport that is needed to maintain alveolar fluid homeostasis during pulmonary edema. We hypothesized that betaAR regulation of alveolar active transport may be mediated via a CFTR dependent pathway.