pyrophosphate and Hypertrophy

Lysophosphatidic acid (LPA) is a bioactive phospholipid with diverse functions mediated via G-protein-coupled receptors (GPCRs). In view of the elevated levels of LPA in acute myocardial infarction (MI) patients we have conducted studies aimed at identifying specific LPA receptor subtypes and signaling events that may mediate its actions in hypertrophic remodeling. Experiments were carried out in cultured neonatal rat cardiomyocytes (NRCMs) exposed to LPA and in a rat MI model. In NRCMs, LPA-induced hypertrophic growth was completely abrogated by DGPP, an LPA1/LPA3 antagonist. The LPA3 agonist OMPT, but not the LPA2 agonist dodecylphosphate, promoted hypertrophy as examined by 3[H]-Leucine incorporation, ANF-luciferase expression and cell area. In in vivo experiments, LPA1, LPA2 and LPA3 mRNA levels as well as LPA1 and LPA3 protein levels increased together with left ventricular remodeling (LVRM) after MI. In addition, LPA stimulated the phosphorylation of Akt and p65 protein and activated NF-kappaB-luciferase expression. Inhibitors of PI3K (wortmannin), mTOR (rapamycin), and NF-kappaB (PDTC or SN50) effectively prevented LPA-induced 3[H]-Leucine incorporation and ANF-luciferase expression. Furthermore, ERK inhibitors (U0126 and PD98059) suppressed LPA-stimulated activation of NF-kappaB and p65 phosphorylation whereas wortmannin showed no effect on NF-kappaB activation. Our findings indicate that LPA3 and/or LPA1 mediate LPA-induced hypertrophy of NRCMs and that LPA1 and LPA3 may be involved in LVRM of MI rats. Moreover, Akt and NF-kappaB signaling pathways independently implicate in LPA-stimulated myocardial hypertrophic growth.

Topics: Animals; Animals, Newborn; Cell Survival; Cells, Cultured; Diphosphates; Enzyme Inhibitors; Female; Glycerol; Hypertrophy; Lysophospholipids; MAP Kinase Signaling System; Myocardial Infarction; Myocytes, Cardiac; NF-kappa B; Organothiophosphates; Phosphatidic Acids; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Receptors, Lysophosphatidic Acid; Signal Transduction; Ventricular Function, Left; Ventricular Remodeling

Changes in the myosin phenotype of differentiated muscle are a prominent feature of the adaptation of the tissue to a variety of physiological stimuli. In the present study the molecular basis of changes in the proportion of myosin isoenzymes in rat skeletal muscle which occur during compensatory hypertrophy caused by the combined removal of synergist muscles and spontaneous running exercise was investigated. The relative amounts of sarcomeric myosin heavy (MHC)- and light (MLC)-chain mRNAs in the plantaris (fast) and soleus (slow) muscles from rats was assessed with cDNA probes specific for different MHC and MLC genes. Changes in the proportion of specific MHC mRNA levels were in the same direction as, and of similar magnitude to, changes in the proportion of myosin isoenzymes encoded for by the mRNAs. No significant changes in the proportion of MLC proteins or mRNA were detected. However, high levels of MLC3 mRNA were measured in both normal and hypertrophied soleus muscles which contained only trace amounts of MLC3 protein. Small amounts of embryonic and neonatal MHC mRNAs were induced in both muscles during hypertrophy. We conclude that the change in the pattern of myosin isoenzymes during skeletal-muscle adaptation to work overload is a consequence of changes in specific MHC mRNA levels.

Topics: Animals; Blotting, Northern; Diphosphates; Electrophoresis, Polyacrylamide Gel; Female; Gene Expression Regulation; Genes; Hypertrophy; Major Histocompatibility Complex; Muscles; Myosins; Rats; Rats, Inbred Strains; RNA, Messenger

Topics: Aged; Bone Diseases; Calcium Pyrophosphate; Crystallization; Diphosphates; Humans; Hypertrophy; Ligaments; Male; Muscular Diseases; Spinal Stenosis

Intense, diffuse localization of Tc-99m-pyrophosphate was demonstrated in the right and left ventricles of a patient with biopsy-proved amyloidosis and severe congestive heart failure. This finding is strong presumptive evidence of myocardial infiltration by amyloid in the presence of biopsy-proven amyloidosis elsewhere in the body.

Topics: Adult; Amyloidosis; Bone and Bones; Diphosphates; Echocardiography; Heart Diseases; Heart Failure; Heart Ventricles; Humans; Hypertrophy; Male; Radioisotopes; Radionuclide Imaging; Technetium; Thallium

Bone-to-bone, iliosacral joint-to-os sacrum and joint-to-joint ratios were computed using the region-of-interest technique 2 to 3 hrs. after injection of 99mTc Sn-methylene-diphosphonate or 99mTc Sn-pyrophosphate in 139 patients with skeletal diseases (bone tumours, degenerative changes of the spine and joints, inflammatory changes of joints) as well as in 123 patients with normal skeletal states. In the latter group, iliosacral joint-to-os sacrum ratios decreased with increasing age of the patients. In patients with osseous metastases of the spine ratios of 0.80 to 4.0 occurred ( reference area second vertebra below or above the affected vertebra). In degenerative changes of the spine values of 0.80 to 1.69 were computed. These results show, that 74% of the spine metastases could not be differentiated from benign changes of the spine by determining their relative amounts of bone uptake. In bone tumours of the extremities and in rheumatoid or gouty arthritis of the small joints (hands and feet) the highest ratios, i.e. contrasts, occurred referring to a contralateral reference area. Osteoarthritic and inflammatory alterations of the big joints could not be differentiated because of percentual distribution of the increased joint-to-joint ratios turned out to be nearly identical.

Topics: Adult; Aged; Arthritis; Arthritis, Rheumatoid; Bone Diseases; Bone Neoplasms; Colonic Neoplasms; Diphosphates; Diphosphonates; Extremities; Femur; Gout; Hemangiosarcoma; Humans; Hypertrophy; Lumbar Vertebrae; Melanoma; Middle Aged; Neoplasm Metastasis; Osteoarthritis; Radionuclide Imaging; Spinal Neoplasms; Spinal Osteophytosis; Spondylolisthesis; Technetium