prostaglandin-h2 and Cardiovascular-Diseases

Isolevuglandins (isoLGs) are extremely reactive gamma-ketoaldehydes that avidly bind covalently with proteins and cause protein-protein as well as DNA-protein crosslinking. IsoLG-protein adducts are generated upon oxidation of low-density lipoprotein (LDL), and may contribute to atherogenesis since such adducts cause recognition and endocytosis of the modified LDL by macrophage cells. Levels of isoLG-protein adducts in human blood plasma are more closely correlated with disease than are the classical risk factors LDL or total cholesterol. We review the basic research that eventuated in the discovery of isoLGs and describe what is known about their natural occurrence and close connection with cardiovascular disease.

Topics: Aldehydes; Animals; Autoantibodies; Cardiovascular Diseases; Free Radicals; Humans; Lipid Peroxidation; Lipoproteins, LDL; Prostaglandin H2; Prostaglandins H; Protein Binding

Thromboxane A2 (TxA2) appears to be an important mediator of ischemia and hypoxia. Despite its short half-life and the fact that it may not circulate in the blood until its values become quite high, TxA2 contributes to the pathogenesis of cardiopulmonary diseases (e.g., sudden death, myocardial ischemia, circulatory shock). It does so because it propagates its own formation by activating platelets and constricting blood vessels, thus activating more TxA2 and trapping it locally within an ischemic or hypoxic region. TxA2 concentrations in the extracellular fluid of lymph of ischemic regions may be much higher than that occurring in nonischemic, normally perfused regions. Specific and potent Tx receptor antagonists (TxRA) have recently become available for study. The TxRA are useful tools in the study of the pathophysiology of Tx-dependent disease processes and have been found to be effective in a variety of ischemic disorders including circulatory shock, myocardial ischemia, and sudden cardiopulmonary death. Moreover, inasmuch as early work indicates that these agents are both safe and effective in humans, Tx receptor antagonists may be employed as therapeutic agents in several cardiovascular disease states. Further investigation is necessary to clarify the role of TxRA as therapeutic agents.

Topics: Animals; Bronchial Spasm; Cardiovascular Diseases; Cell Membrane; Humans; Hypoxia; Ischemia; Platelet Aggregation; Prostaglandin Endoperoxides, Synthetic; Prostaglandin H2; Prostaglandins H; Receptors, Prostaglandin; Receptors, Thromboxane; Vasoconstriction