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Ulrike Hampel, Katharina Träger, Hanhan Liu, Julia Teister, Franz Grus, Verena Prokosch-Willing
PURPOSE: Recently, the vasodilator relaxin 2 has been introduced as a treatment for acute heart failure. However, its role on vessels of the eye and intraocular pressure (IOP) remains unclear though it has been hypothesized to induce a decrease IOP after intramuscular injection in humans. We aimed to test whether the hormone relaxin 2 lowers IOP and dilates retinal vessels in animals. METHODS: The IOP of female Sprague-Dawley rats before and after application of relaxin 2 was measured using an Icare Tonolab device calibrated for rats...
March 13, 2018: International Ophthalmology
Sarah A Marshall, Jonathan T McGuane, Yu May Soh, Helen M Gehring, Emma Simpson, Laura J Parry
Relaxin regulates cervical extracellular matrix (ECM) remodelling during pregnancy by modifying collagen and other ECM molecules by unknown mechanisms. We hypothesised that abnormal collagen remodelling in the cervix of pregnant relaxin-deficient (Rln1-/-) mice is due to excessive collagen (Col1a1 and Col3a1) and decreased matrix metalloproteinases (Mmp2, Mmp9, Mmp13 and Mmp7) and oestrogen receptors (Esr1 and Esr2). Quantitative polymerase chain reaction, gelatinase zymography, MMP activity assays and histological staining evaluated changes in ECM in pregnant wildtype (Rln1+/+) and Rln1-/- mice...
March 14, 2018: Reproduction, Fertility, and Development
Teja Devarakonda, Fadi N Salloum
The hormone relaxin has long been recognized for its involvement in maternal adaptation during pregnancy. However, discoveries during the past two decades on the mechanism of action of relaxin, its family of receptors, and newly described roles in attenuating ischemia/reperfusion (I/R) injury, inflammation, and arrhythmias have prompted vast interest in exploring its therapeutic potential in cardiovascular disease. These observations inspired recently concluded clinical trials in patients with acute heart failure...
March 8, 2018: Trends in Endocrinology and Metabolism: TEM
Y Xu, Q Yu, Y Liu
No abstract text is available yet for this article.
March 7, 2018: British Journal of Biomedical Science
Eglantina Idrizaj, Rachele Garella, Fabio Francini, Roberta Squecco, Maria Caterina Baccari
AIM: To investigate the signaling pathways involved in the relaxin (RLX) effects on ileal preparations from mice through mechanical and electrophysiological experiments. METHODS: For mechanical experiments, ileal preparations from female mice were mounted in organ baths containing Krebs-Henseleit solution. The mechanical activity was recorded via force-displacement transducers, which were coupled to a polygraph for continuous recording of isometric tension. Electrophysiological measurements were performed in current- and voltage-clamp conditions by a microelectrode inserted in a single smooth muscle cell (SMC) of the ileal longitudinal layer...
February 28, 2018: World Journal of Gastroenterology: WJG
Seema Dubey, Hyunho Yoon, Mark Steven Cohen, Prakash Nagarkatti, Mitzi Nagarkatti, Dev Karan
A role of inflammation-associated cytokines/chemokines has been implicated in a wide variety of human diseases. Here, we investigated the regulation of inflammatory cytokines released by monocyte-derived THP-1 cells following treatment with the dietary agent withaferin A (WFA). Membrane-based cytokine array profiling of the culture supernatant from adenosine triphosphate-stimulated WFA-treated THP-1 cells showed differential regulation of multiple cytokines/chemokines. A selected group of cytokines/chemokines [interleukin-1 beta (IL-1β), CCL2/MCP-1, granulocyte-macrophage colony stimulating factor, PDGF-AA, PTX3, cystatin-3, relaxin-2, TNFRSF8/CD30, and ACRP30] was validated at the transcription level using qPCR...
2018: Frontiers in Immunology
Alexander Zaykov, Vasily Gelfanov, Fa Liu, Richard Dennis DiMarchi, Richard Dennis DiMarchi
We report the synthesis and in vitro bioactivity assessment for an insulin-like peptide 5 (INSL5) analog that was recently discovered as a genetic mutation in an Amish population. The mutation was associated with improved metabolic status and receptor-based antagonism was proposed as a potential mechanism for the altered phenotype. We determined the specific peptide analog to be fully potent and of maximal efficacy at the human relaxin family peptide receptor 4 (RXFP-4), suggesting an alternative basis for the observed effect...
February 21, 2018: ChemMedChem
Ross A D Bathgate, Martina Kocan, Daniel J Scott, M Akhter Hossain, Sara V Good, Sergey Yegorov, Jan Bogerd, Paul Gooley
The peptide relaxin was first identified as an important circulating hormone during pregnancy over 90 years ago. Research over many years defined the numerous biological roles that relaxin plays throughout pregnancy in many mammalian species. These important biological actions have led to the testing of relaxin as a therapeutic agent for a number of indications. The discovery of the relaxin receptor, RXFP1, in 2002 facilitated the better understanding of the cellular targets of relaxin, its mechanism of action and enabled the development of relaxin mimetics and screening for small molecule agonists...
February 16, 2018: Pharmacology & Therapeutics
Maggie Lam, Simon G Royce, Chrishan S Samuel, Jane E Bourke
The most common therapies for asthma and other chronic lung diseases are anti-inflammatory agents and bronchodilators. While these drugs oppose disease symptoms, they do not reverse established structural changes in the airways and their therapeutic efficacy is reduced with increasing disease severity. The peptide hormone, relaxin, is a Relaxin Family Peptide Receptor 1 (RXFP1) receptor agonist with unique combined effects in the lung that differentiates it from these existing therapies. Relaxin has previously been reported to have cardioprotective effects in acute heart failure as well anti-fibrotic actions in several organs...
February 12, 2018: Pharmacology & Therapeutics
Xiangyu Gao, Hongwei Li, Ping Wang, Hui Chen
Circulating relaxin (RLX) is altered in patients with diabetes mellitus (DM) or cardiovascular diseases. This study was designed to evaluate the changes of RLX in patients with unstable angina (UA) complicated with various categories of abnormal glucose metabolism.Patients who confirmed UA by angiographic and clinical standard were grouped according to the glucose metabolism status with oral glucose tolerance test (OGTT) and medical history categorized as normal, prediabetes, newly diagnosed type 2 DM (T2DM), and previously diagnosed T2DM...
February 14, 2018: International Heart Journal
Maria Jelinic, Sarah A Marshall, Dennis Stewart, Elaine Unemori, Laura J Parry, Chen Huei Leo
The peptide hormone relaxin has numerous roles both within and independent of pregnancy and is often thought of as a 'pleiotropic hormone'. Relaxin targets several tissues throughout the body, and has many functions associated with extracellular matrix remodeling and the vasculature. This review considers the potential therapeutic applications of relaxin in cervical ripening, in vitro fertilization, preeclampsia, acute heart failure, ischemia-reperfusion and cirrhosis. We first outline the animal models used in preclinical studies to progress relaxin into clinical trials and then discuss the findings from these studies...
February 7, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
A Aragón-Herrera, S Feijóo-Bandín, D Rodríguez-Penas, E Roselló-Lletí, M Portolés, M Rivera, M Bigazzi, D Bani, O Gualillo, J R González-Juanatey, F Lago
PURPOSE: Many evidences show that the hormone relaxin plays a pivotal role in the physiology and pathology of the cardiovascular system. This pleiotropic hormone exerts regulatory functions through specific receptors in cardiovascular tissues: in experimental animal models it was shown to induce coronary vasodilation, prevent cardiac damage induced by ischemia/reperfusion and revert cardiac hypertrophy and fibrosis. A tight relationship between this hormone and important metabolic pathways has been suggested, but it is at present unknown if relaxin could regulate cardiac metabolism...
February 6, 2018: Endocrine
Jane F Reckelhoff
PURPOSE OF REVIEW: The review is a short discussion of sex/gender differences in blood pressure control with a focus on gender differences in hypertension awareness, prevalence, and treatment, the new American College of Cardiology/American Heart Association Guidelines, and recent discoveries in animal models and humans on mechanisms responsible for sex/gender differences in hypertension. RECENT FINDINGS: Hypertension awareness is greater in women than men, the prevalence of hypertension is higher in men than women until after menopause, and although the American College of Cardiology/American Heart Association Guidelines recommend similar treatment for men and women, this is not currently the case in practice...
February 5, 2018: Current Opinion in Nephrology and Hypertension
Xiao Wei, Yuan Yang, Yin-Jiu Jiang, Jian-Ming Lei, Jing-Wen Guo, Hua Xiao
The present study aimed to investigate the role of relaxin (RLX) on high glucose (HG)-induced cardiomyocyte hypertrophy and apoptosis, as well as the possible molecular mechanism. H9c2 cells were exposed to 33 mmol/l HG with or without RLX (100 nmol/ml). Cell viability, apoptosis, oxidative stress, cell hypertrophy and the levels of Notch1, hairy and enhancer of split 1 (hes1), atrial natriuretic polypeptide (ANP), brain natriuretic peptide (BNP), manganese superoxide dismutase (MnSOD), cytochrome C and caspase-3 were assessed in cardiomyocytes...
January 2018: Experimental and Therapeutic Medicine
Marta Nowak, Alois Boos, Mariusz P Kowalewski
By acting through its receptors (RXFP1, RXFP2), relaxin (RLN) exerts species-specific effects during pregnancy; possible luteotropic effects through stimulation of prolactin (PRL) release have been suggested. In the domestic dog (Canis lupus familiaris) serum PRL increases in pregnant bitches shortly after RLN appears in the circulation, and a possible functional relationship between the RLN and the PRL systems in regulating progesterone secretion has been implied. Therefore, here (Study 1) the luteal expression and localization of the RLN system was investigated by immunohistochemistry using custom-made antibodies and semi-quantitative PCR, at selected time points during gestation: pre-implantation (d...
2018: PloS One
Shoichi Kageyama, Kojiro Nakamura, Takehiro Fujii, Bibo Ke, Rebecca A Sosa, Elaine F Reed, Nakul Datta, Ali Zarrinpar, Ronald W Busuttil, Jerzy W Kupiec-Weglinski
Hepatic ischemia-reperfusion injury (IRI) represents a major risk factor of early graft dysfunction and acute/chronic rejection as well as a key obstacle to expanding the donor pool in orthotopic liver transplantation (OLT). Although glucocorticoid receptor (GR) signaling may enhance cytoprotective programs, clinical use of glucocorticoid is limited due to adverse effects, while clinical relevance of GR-facilitated cytoprotection in OLT remains unknown. We aimed to evaluate the significance of hepatic GR in clinical OLT and verify the impact of recombinant human relaxin (rhRLX), which may function as GR agonist in tissue/disease-specific manner...
January 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Brian Martin, Beth Ann Gabris-Weber, Rajiv Reddy, Guillermo Romero, Ansuman Chattopadhyay, Guy Salama
BACKGROUND: 'Healthy' aging drives structural and functional changes in the heart including maladaptive electrical remodeling, fibrosis and inflammation, which lower the threshold for cardiovascular diseases such as heart failure (HF) and atrial fibrillation (AF). Despite mixed results in recent clinical trials, Relaxin-therapy for 2-days could reduce mortality by 37% at 180-days post-treatment, in patients with acute decompensated HF. Relaxin's short life-span (hours) but long-lasting protective actions led us to test the hypothesis that relaxin acts at a genomic level to reverse maladaptive remodeling in aging and HF...
2018: PloS One
Massimo Venditti, Aldo Donizetti, Marcella Fiengo, Chiara Fasano, Alessandra Santillo, Francesco Aniello, Sergio Minucci
Relaxin (RLN) and insulin (INSL)-like peptides are member of the INSL/RLN superfamily, which are encoded by seven genes in humans and can activate the G-protein coupled receptor RXFP 1-4. These peptides evolved from a common ancestor, RLN3-like gene. Two rounds of whole genome duplication (WGD) in early vertebrate evolution, together with an additional WGD in the teleost lineage, caused an expansion of RLN genes set in the genome of Danio rerio. In particular, six RLN genes are present: a single copy of rln and insl3 genes, and two paralogs for the rln3 gene (rln3a and rln3b), and the insl5 gene (insl5a and insl5b)...
January 10, 2018: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
Xiaohui Zhang, Yu Fu, Hui Li, Li Shen, Qing Chang, Liya Pan, Siting Hong, Xinhua Yin
Excessive production of reactive oxygen species (ROS) and P2X7R activation induced by high glucose increases NLRP3 inflammasome activation, which contributes to the pathogenesis of diabetic cardiomyopathy. Although H3 relaxin has been shown to inhibit cardiac fibrosis induced by isoproterenol, the mechanism has not been well studied. Here, we demonstrated that high glucose (HG) induced the collagen synthesis by activation of the NLRP3 inflammasome, leading to caspase-1 activation, interleukin-1β (IL-1β) and IL-18 secretion in neonatal rat cardiac fibroblasts...
January 5, 2018: Journal of Cellular and Molecular Medicine
Juan Cui, Yanguo Liu, Xiuwen Wang
Glycodelin is a kind of glycoprotein expressed in secretory endometrium, pregnancy deciduas, and amniotic fluid originally, which is vital for the maintenance of normal human reproductive activities. Recent researches have reported that glycodelin is specifically expressed in various malignancies, including female-specific cancers such as endometrial cancer, ovarian cancer and breast cancer, and non-gender specific cancers including lung cancer, and colon cancer, and glycodelin expression correlates with the diagnosis and prognosis of cancer patients...
2017: Frontiers in Immunology
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