endothelin-1 and Disease

The accumulation of unfolded proteins in the endoplasmic reticulum (ER) represents a cellular stress induced by multiple stimuli and pathologic conditions. Recent evidence implicates endothelin-1 (ET-1) in the induction of placental ER stress in pregnancy disorders. ER stress has previously also been implicated in various other disease states, including neurodegenerative disorders, diabetes, and cardiovascular diseases, as has ET-1 in the pathophysiology of these conditions. However, to date, there has been no investigation of the link between ET-1 and the induction of ER stress in these disease states. Based on recent evidence and mechanistic insight into the role of ET-1 in the induction of placental ER stress, the following review attempts to outline the broader implications of ET-1-induced ER stress, as well as strategies for therapeutic intervention based around ET-1.

Topics: Animals; Cardiovascular Diseases; Diabetes Mellitus; Disease; Endoplasmic Reticulum Stress; Endothelin Receptor Antagonists; Endothelin-1; Female; Humans; Nerve Degeneration; Pregnancy; Pregnancy Complications

Endothelin-1 (ET-1), a member of endothelin peptide family is released by many different tissues including uterine smooth muscle. ET-1 acts through ETA and ETB receptors and is implicated in a wide range of biological and pathological functions that explain the great attention of the pharmacological industry for ET-1 receptors as potential therapeutic targets in vascular pathologies and cancers. It is now well established that ET-1 is also able to regulate myometrial functions. In the present review, we focused on ET axis and related signaling pathways involved in the regulation of myometrial contraction, as well as cell proliferation and survival. Such ET-1-mediated cellular functions play a critical role in normal pregnancy, preterm birth and uterine leiomyoma.

Topics: Amino Acid Sequence; Disease; Endothelin-1; Female; Humans; Molecular Sequence Data; Myometrium; Signal Transduction; Uterine Contraction

1. There is an ever increasing volume of evidence implicating endothelin-1 and its isoforms in a range of disease processes. These include asthma, pulmonary and essential systemic hypertension, cardiac failure and uterine dysfunction. 2. However, it is also important to realize that the endothelins play an obligatory role in normal cellular proliferation, repair and tissue development. 3. The present brief review focuses on some of the physiological and pathophysiological mediator roles of the endothelins and provides a sketch of the receptor systems and some of the signal transduction pathways that are now known to operate following receptor activation. 4. Importantly, it is now clear that the endothelins, their receptors and synthesis and degradation pathways offer potentially important therapeutic targets.

Topics: Disease; Endothelin-1; Endothelins; Humans; Muscle, Smooth; Receptors, Endothelin; Signal Transduction

Endothelin-1 (ET-1) undergoes an about 8-h (circaoctohoran) rather than a circadian variation in clinical health. Herein, 24 h plasma concentrations of vasoactive intestinal peptide (VIP), substance P (SP), neuropeptide Y (NpY), and cortisol used as reference, were obtained from 20 healthy young adults starting at 07:00 or 19:00 h. Like ET-1, SP and NpY undergo a circaoctohoran variation, whereas VIP is circadian rhythmic, peaking during the night, some 8 h prior to the circadian acrophase of cortisol. Maps of circadian and extra-circadian patterns may serve for screening, diagnosis and a better understanding of mechanisms underlying the etiology of various diseases.

Topics: Adult; Circadian Rhythm; Diagnosis; Disease; Endothelin-1; Female; Humans; Hydrocortisone; Male; Neuropeptide Y; Substance P; Vasoactive Intestinal Peptide