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Cardiovascular pharmacology

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https://www.readbyqxmd.com/read/27924341/structure-activity-relationship-of-novel-macrocyclic-biased-apelin-receptor-agonists
#1
Alexandre Murza, Xavier Sainsily, Jérôme Côté, Laurent Bruneau-Cossette, Élie Besserer-Offroy, Jean-Michel Longpré, Richard Leduc, Robert Dumaine, Olivier Lesur, Mannix Auger-Messier, Philippe Sarret, Éric Marsault
Apelin is the endogenous ligand for the G protein-coupled receptor APJ and exerts a key role in regulating cardiovascular functions. We report herein a novel series of macrocyclic analogues of apelin-13 in which the N- and C-terminal residues as well as the macrocycle composition were chemically modified to modulate structure-activity relationships on the APJ receptor. To this end, the binding affinity and the ability to engage G protein-dependent and G protein-independent signalling pathways of the resulting analogues were assessed...
December 7, 2016: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/27923790/dynamin-related-protein-1-mediates-low-glucose-induced-endothelial-dysfunction-in-human-arterioles
#2
Michael John Tanner, Jingli Wang, Rong Ying, Tisha B Suboc, Mobin Malik, Allison Couillard, Amberly Branum, Venkata Puppala, Michael Eric Widlansky
Intensive glycemic regulation has resulted in an increased incidence of hypoglycemia. Hypoglycemic burden correlates with adverse cardiovascular complications and contributes acutely and chronically to endothelial dysfunction. Prior data indicate mitochondrial dysfunction contributes to hypoglycemia-induced endothelial dysfunction, but the mechanisms behind this linkage remain unknown. We attempt to determine whether clinically relevant low glucose (LG) exposures acutely induce endothelial dysfunction through activation of the mitochondrial fission process...
December 6, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27923281/nuclear-factor-erythroid-derived-2-like-2-and-thioredoxin-1-in-atherosclerosis-and-ischemia-reperfusion-injury-in-the-heart
#3
Philipp Jakobs, Vlad Serbulea, Norbert Leitinger, Anna Eckers, Judith Haendeler
Significance Redox signaling is one of the key elements involved in cardiovascular diseases. Two important molecules are the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) and the oxidoreductase Thioredoxin-1 (Trx-1). Recent Advances During the last years, a lot of studies investigated Nrf2 and Trx-1 as protective proteins in cardiovascular disorders. Moreover, post-translational modifications of those molecules were identified which play an important role in the cardiovascular system...
December 6, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27921437/-adaptation-of-adipose-tissue-to-weight-reduction-energy-restricted-diet-in-obese-individuals
#4
Vladimír Štich
Obesity is associated with a number of metabolic disorders that lead to the development of type 2 diabetes, hyperlipidemia and ultimately cardiovascular diseases. An important role in the pathogenesis of metabolic disorders accompanying obesity is probably played by the alterations of adipose tissue characteristics: metabolic, endocrine and immune functions. The key component of obesity treatment, the weight-reduction energy-restricted diet, leads not only to the reduction of weight (specifically fat mass), but also to correction of obesity accompanying metabolic disorders...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27921047/pharmacological-interventions-against-obesity-current-status-and-future-directions
#5
REVIEW
Bernd Schultes
The metabolic syndrome (MS) comprises a cluster of metabolic disturbances including obesity, hyperglycemia, dyslipidemia, and elevated blood pressure that are pathophysiologically highly interlinked and that altogether lead to an increased cardiovascular (CV) risk. While lifestyle interventions represent the basic therapeutic measure to address all components of the MS, they are in most cases not effective enough to reduce the CV risk. Therefore, pharmacological interventions are necessary for many patients...
October 2016: Visceral Medicine
https://www.readbyqxmd.com/read/27920820/protective-effect-of-melissa-officinalis-extract-against-h2o2-induced-oxidative-stress-in-human-vascular-endothelial-cells
#6
Leila Safaeian, Seyyed Ebrahim Sajjadi, Shaghayegh Haghjooy Javanmard, Hossein Montazeri, Fariba Samani
Melissa officinalis L. is a medicinal plant with a large variety of pharmacological effects and traditional applications. This study aimed to evaluate the protective and antioxidant activities of the extract of M. officinalis aerial parts on human umbilical vein endothelial cells (HUVECs) under oxidative stress induced by H2O2. Cells were incubated with H2O2 (0.5 mM, 2 h) after pretreatment with M. officinalis extract (25-500 μg/mL). Cell viability was evaluated by 3-(4, 5- Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay...
October 2016: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27917712/the-role-of-antiplatelet-therapy-in-primary-prevention-a-review
#7
Lauge Østergaard, Emil L Fosbøl, Matthew T Roe
The efficacy of antiplatelet therapy for the secondary prevention of cardiovascular disease after an ischemic event is well established. However, the role for antiplatelet therapy for the primary prevention of cardiovascular disease is more complex because of the interplay of efficacy vs safety in individuals without established cardiovascular disease who have a relatively low, but linear trajectory of cardiovascular risk. Several large randomized trials have investigated the efficacy and safety of antiplatelet therapy (primarily aspirin) for patients without established cardiovascular disease...
December 5, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27916655/allopurinol-as-a-therapeutic-option-in-cardiovascular-disease
#8
REVIEW
Osita N Okafor, K Farrington, Diana A Gorog
Epidemiological studies indicate that hyperuricaemia is an independent risk factor for cardiovascular disease. Alongside uric acid formation, increased xanthine oxidase activity also results in the formation of oxidative free radicals and superoxide particles. Oxidative stress significantly contributes to the development of cardiovascular disease, including endothelial cell dysfunction, atherosclerosis, vascular calcification and impaired myocardial energetics. Allopurinol, a competitive xanthine oxidase inhibitor, in addition to reducing serum uric acid levels, can act as a free radical scavenger...
December 1, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27914706/vascular-calcification-in-chronic-kidney-disease-different-bricks-in-the-wall
#9
REVIEW
Marc Vervloet, Mario Cozzolino
A high prevalence of vascular calcification (VC) and a high incidence of cardiovascular events are two key complications of chronic kidney disease. Since most observational studies found a positive association between these two complications, a causal relationship has been assumed. If so, this would render VC a target of therapy. Recent studies, however, suggested this assumption might be an oversimplification. The fundamental aspects of these recent studies are two-fold. The first novel insight is that VC is not a single entity...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27913272/the-northeast-regional-sps-meeting-update-safety-pharmacology-innovations-and-applications
#10
REVIEW
Malar Pannirselvam, Tiffini Brabham, Alfred W Botchway, Donald B Hodges, Martin Traebert, Michael K Pugsley
The Safety Pharmacology Society (SPS) held a Northeast (NE) regional meeting in Boston, MA on May 13, 2016 at the Vertex Pharmaceuticals Incorporated site. There were 103 attendees from the pharmaceutical industry, contract research organizations (CROs), academia, and global regulatory agencies. An assortment of scientific topics were presented by 7 speakers that included broad topics in the cardiovascular (organ on chip, statistical power and translation of rat cardiovascular telemetry data and dual inhibition of IKr and IKs on QT interval prolongation) and central nervous system (in vitro platform for neurotoxicity, an integrated risk assessment of suicidal ideation and behavior, and EEG advances in safety pharmacology) and a novel topic discussing preclinical challenges faced in the development of a novel gene therapy...
November 29, 2016: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/27909989/orexin-and-central-modulation-of-cardiovascular-and-respiratory-function
#11
Pascal Carrive, Tomoyuki Kuwaki
Orexin makes an important contribution to the regulation of cardiorespiratory function. When injected centrally under anesthesia, orexin increases blood pressure, heart rate, sympathetic nerve activity, and the amplitude and frequency of respiration. This is consistent with the location of orexin neurons in the hypothalamus and the distribution of orexin terminals at all levels of the central autonomic and respiratory network. These cardiorespiratory responses are components of arousal and are necessary to allow the expression of motivated behaviors...
December 2, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27909712/myocardial-perfusion-spect-2015-in-germany-results-of-the-7th-survey
#12
Oliver Lindner, Wolfgang Burchert, Wolfgang Schäfer, Marcus Hacker
AIM: The working group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine presents the results of the 7th survey of myocardial perfusion SPECT (MPS) of the reporting year 2015. METHOD: 268 questionnaires (173 practices [PR], 67 hospitals [HO], 28 university hospitals [UH]) were evaluated. Results of the last survey from 2012 are set in squared brackets. RESULTS: MPS of 121 939 [105 941] patients were reported. 98 % [95 %] of all MPS were performed with Tc-99m radiopharmaceuticals and 2 % [5 %] with Tl-201...
December 2, 2016: Nuklearmedizin. Nuclear Medicine
https://www.readbyqxmd.com/read/27908822/how-admission-to-a-vascular-surgery-department-improves-medical-treatment-in-patients-with-lower-extremity-peripheral-arterial-disease
#13
M Thiney, N Della Schiava, P Feugier, P Lermusiaux, J Ninet, A Millon, A Long
OBJECTIVES: All patients with lower extremity peripheral arterial disease (LE-PAD) should benefit from recommended pharmacologic therapies including antiplatelet agents, angiotensin converting enzyme (ACE) inhibitors or Angiotensin receptor blockers (ARBs), and HMG-CoA-reductase inhibitors (statins). In the present study, this triple therapy was defined as the best medical treatment. This study was designed to determine the number of patients who received best medical treatment at admission and at discharge from a vascular surgery department...
November 28, 2016: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/27907893/factors-impacting-complication-rates-for-catheter-ablation-of-atrial-fibrillation-from-2003-to-2015
#14
Eunice Yang, Esra Gucuk Ipek, Muhammad Balouch, Yuliya Mints, Jonathan Chrispin, Joseph E Marine, Ronald D Berger, Hiroshi Ashikaga, Jack Rickard, Hugh Calkins, Saman Nazarian, David D Spragg
AIMS: Complications from catheter ablation for atrial fibrillation (AF) are well described. Changing aspects of AF ablation including patient populations referred, institutional experience, and emerging catheter and pharmacological options may impact complication rates. We assessed procedural complication trends in AF ablation patients from 2003-2015 to identify what factors affect adverse event rates. METHODS AND RESULTS: We evaluated consecutively enrolled patients undergoing initial AF ablation from 2003 through 2015...
October 6, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/27904522/inducing-apolipoprotein-a-i-synthesis-to-reduce-cardiovascular-risk-from-assert-to-sustain-and-beyond
#15
Belinda A Di Bartolo, Daniel J Scherer, Stephen J Nicholls
Increasing attention has focused on efforts to promote the biological activities of high-density lipoproteins (HDL) in order to reduce cardiovascular risk. Targeting apolipoprotein A-I (apoA-I), the major protein carried on HDL particles, represents an attractive approach to promoting HDL by virtue of its ability to increase endogenous synthesis of functional HDL particles. A number of pharmacological strategies that target apoA-I, including upregulation of its production with the bromodomain and extraterminal (BET) protein inhibitor RVX-208, development of short peptide sequences that mimic its action, and administration as a component of reconstituted HDL particles, have undergone clinical development...
December 1, 2016: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/27904032/coronary-microvascular-dysfunction%C3%A3-epidemiology-pathogenesis-prognosis-diagnosis-risk-factors-and-therapy
#16
Cheng Chen, Janet Wei, Ahmed AlBadri, Parham Zarrini, C Noel Bairey Merz
Angina has traditionally been thought to be caused by obstructive coronary artery disease (CAD). However, a substantial number of patients with angina are found to not have obstructive CAD when undergoing coronary angiography. A significant proportion of these patients have coronary microvascular dysfunction (CMD), characterized by heightened sensitivity to vasoconstrictor stimuli and limited microvascular vasodilator capacity. With the advent of non-invasive and invasive techniques, the coronary microvasculature has been more extensively studied in the past 2 decades...
November 29, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/27903214/chemotherapy-and-cardiotoxicity-in-hematologic-malignancies-a-review
#17
Antonio Stellitano, Roberta Fedele, Santina Barillà, Antonino Iaria, Carmelo Massimiliano Rao, Massimo Martino
Antineoplastic agents affect the cardiovascular system, and the incidence of cardiotoxicity is continuously growing in patients with hematologic malignancies and treated with antineoplastic therapy. Cardio-oncology is a quite young discipline, designed for diagnosis, prevention and treatment of cardiovascular complications of anticancer agents. Nowadays, with the current treatments and an accurate pharmacological control of comorbidities present at the time of the oncological diagnosis, early clinical events are infrequent, and it seems indeed that cardiotoxicity could emerge as time and years go by, after therapies completion...
November 21, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27900610/novel-sgc-stimulators-and-sgc-activators-for-the-treatment-of-heart-failure
#18
Stefanie Breitenstein, Lothar Roessig, Peter Sandner, Kelly S Lewis
The burden of heart failure (HF) increases worldwide with an aging population, and there is a high unmet medical need in both, heart failure with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). The nitric oxide (NO) pathway is a key regulator in the cardiovascular system and modulates vascular tone and myocardial performance. Disruption of the NO-cyclic guanosine monophosphate (cGMP) signaling axis and impaired cGMP formation by endothelial dysfunction could lead to vasotone dysregulation, vascular and ventricular stiffening, fibrosis, and hypertrophy resulting in a decline of heart as well as kidney function...
November 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27897416/curcumin-an-effective-adjunct-in-patients-with-statin-associated-muscle-symptoms
#19
REVIEW
Amirhossein Sahebkar, Nikou Saboni, Matteo Pirro, Maciej Banach
In spite of the unequivocal efficacy of statins in reducing primary and secondary cardiovascular events, the use of these drugs in a considerable number of patients is limited because of statin intolerance, mainly statin-associated muscle symptoms (SAMS). SAMS encompass a broad spectrum of clinical presentations, including mild muscular aching and other types of myalgias, myopathy with the significant elevation of creatine kinase, and the rare but life-threatening rhabdomyolysis. Among several pathophysiologic mechanisms of SAMS, mitochondrial dysfunction is thought to be one of the main one...
September 22, 2016: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27896943/ang-1-7-protects-cardiomyocytes-against-hg-induced-injuries-through-inhibiting-ros-activated-leptin-p38-mapk-erk1-2-pathways-but-not-leptin-jnk-pathway-in-vitro
#20
Yiyan Lei, Qing Xu, Bo Zeng, Wei Zhang, Yulan Zhen, Yuansheng Zhai, Fei Cheng, Weiyi Mei, Dongdan Zheng, Jianqiang Feng, Jun Lan, Jingfu Chen
AIMS: Angiotensin-(1-7) [Ang-(1-7)], recognized as a new bioactive peptide in renin-angiotensin system (RAS), shows biological and pharmacological properties in diabetic cardiovascular diseases. Leptin induced-p38 MAPK pathway has been reported to contribute to the high glucose (HG)-induced injury. In this study, we demonstrated the mechanism that how Ang-(1-7) can protect from HG-stimulated injuries in H9c2 cells. METHODS: H9c2 cells were treated with 35 mM glucose (HG) for 24 h to establish a model of HG-induced damage...
November 29, 2016: Journal of Diabetes Investigation
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