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https://www.readbyqxmd.com/read/28932625/vascular-aging-implications-for-cardiovascular-disease-and-therapy
#1
Yohannes T Ghebre, Eduard Yakubov, Wing Tak Wong, Prasanna Krishnamurthy, Nazish Sayed, Andrew G Sikora, Mark D Bonnen
The incidence and prevalence of cardiovascular disease is highest among the elderly, in part, due to deleterious effects of advancing age on the heart and blood vessels. Aging, a known cardiovascular risk factor, is progressively associated with structural and functional changes to the vasculature including hemodynamic disturbance due to increased oxidative stress, premature cellular senescence and impairments in synthesis and/or secretion of endothelium-derived vasoactive molecules. These molecular and physiological changes lead to vessel wall stiffening and thickening, as well as other vascular complications that culminate to loss of vascular tone regulation and endothelial function...
December 2016: Translational Medicine: Current Research
https://www.readbyqxmd.com/read/28926093/pulmonary-hypertension-molecular-aspects-of-current-therapeutic-intervention-and-future-direction
#2
Taruna Katyal Arora, Amit KumarArora, Monika Katyal Sachdeva, Satyendra Kumar Rajput, Arun Kumar Sharma
Pulmonary hypertension (PH) is a life-threatening lung disorder with towering prevalence and risk for future has been gradually rising worldwide. Even, no specific medications are available for pulmonary hypertension; various classes of treatment based upon the origin and magnitude of hypertension are still used for the treatment of PH. Consideration of molecular or signaling modulation is the imperative approach that can offer a new notion for prevalent pharmacotherapeutic agents. Instead of concurrent targets, including endothelin receptor antagonists (ETA/ETB), phosphodiesterase 5 inhibitor (PDF-5), calcium channel blockers, anticoagulants, diuretics and long acting prostacyclin analogue, recent scientific reports revealed the numerous potential alternative therapeutic approaches that can significantly target the pathological signaling alteration associated with PH...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28922437/molecular-biomarkers-as-predictors-for-biliary-complications-following-liver-transplantation-a-prospective-study
#3
Bogdan Dorobantu, Irinel Popescu, Simona Dima, Anca Nastase, Speranta Iacob
BACKGROUND: The biliary complications (BC) have been always considered the "Achilles' heel" of liver transplantation (LT), being one of the leading causes of postoperative morbidity. AIM: To analyse predictors of BC, by monitoring in the peripheral blood the biomarkers involved in the inflammation and hepatic fibrosis, such as the matrix metalloproteinases (MMP 2, 9) and their tissue inhibitors (TIMP1), the interleukins (IL 2, 8), alfa-TNF, the endothelins and their receptors...
September 2017: Journal of Gastrointestinal and Liver Diseases: JGLD
https://www.readbyqxmd.com/read/28915577/vorinostat-suppresses-hypoxia-signaling-by-modulating-nuclear-translocation-of-hypoxia-inducible-factor-1-alpha
#4
Chao Zhang, Chunzhang Yang, Michael J Feldman, Herui Wang, Ying Pang, Dominic M Maggio, Dongwang Zhu, Cody L Nesvick, Pauline Dmitriev, Petra Bullova, Prashant Chittiboina, Roscoe O Brady, Karel Pacak, Zhengping Zhuang
Histone deacetylase inhibitors (HDACis) are a potent class of tumor-suppressive agents traditionally believed to exert their effects through loosening tightly-wound chromatin resulting in de-inhibition of various tumor suppressive genes. Recent literature however has shown altered intratumoral hypoxia signaling with HDACi administration not attributable to changes in chromatin structure. We sought to determine the precise mechanism of HDACi-mediated hypoxia signaling attenuation using vorinostat (SAHA), an FDA-approved class I/IIb/IV HDACi...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28891448/a-special-focus-on-selexipag-treatment-of-pulmonary-arterial-hypertension
#5
Louise Marqvard Sørensen, Markus Wehland, Marcus Krüger, Ulf Simonsen, Mohamed Zakaria Nassef, Manfred Infanger, Daniela Grimm
BACKGROUND: This review focuses on the treatment of pulmonary arterial hypertension (PAH) with selexipag and compares its drug-related therapeutic effects with those of prostacyclin analogues. METHODS: We searched the relevant literature and summarized the current clinical trials concerning selexipag and PAH. RESULTS: With only few cases per million, PAH is a rare disease, but when untreated it can be life threatening. PAH is linked to elevated levels of endothelin (ET-1) and decreased levels of nitric oxide (NO) and prostacyclin (PGI2)...
September 7, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28889107/respite-switching-to-riociguat-in-pulmonary-arterial-hypertension-patients-with-inadequate-response-to-phosphodiesterase-5-inhibitors
#6
Marius M Hoeper, Gérald Simonneau, Paul A Corris, Hossein-Ardeschir Ghofrani, James R Klinger, David Langleben, Robert Naeije, Pavel Jansa, Stephan Rosenkranz, Laura Scelsi, Ekkehard Grünig, Carmine Dario Vizza, MiKyung Chang, Pablo Colorado, Christian Meier, Dennis Busse, Raymond L Benza
A proportion of pulmonary arterial hypertension (PAH) patients do not reach treatment goals with phosphodiesterase-5 inhibitors (PDE5i). RESPITE investigated the safety, feasibility and benefit of switching from PDE5i to riociguat in these patients.RESPITE was a 24-week, open-label, multicentre, uncontrolled study. Patients in World Health Organization (WHO) functional class (FC) III, with 6-min walking distance (6MWD) 165-440 m, cardiac index <3.0 L·min(-1)·m(-2) and pulmonary vascular resistance >400 dyn·s·cm(-5) underwent a 1-3 day PDE5i treatment-free period before receiving riociguat adjusted up to 2...
September 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28882485/zinc-chloride-rapidly-stimulates-efflux-transporters-in-renal-proximal-tubules-of-killifish-fundulus-heteroclitus
#7
Alexander Zaremba, David S Miller, Gert Fricker
Multidrug resistance-related protein 2 (Mrp2) is an ATP-driven efflux pump at the luminal membrane in renal proximal tubules. It acts as detoxification mechanism by transporting xenobiotics and metabolic products into urine. The trace element zinc is essential for cellular growth, differentiation and survival. It modulates immune response and is used as dietary supplement. Here, we found that 0.1-10μM ZnCl2 rapidly stimulated transport of the Mrp2 probe substrate Texas Red (TR) in isolated killifish renal proximal tubules, which provide an established model system to measure efflux transporter activity by using fluorescent probe substrates, confocal microscopy and image analysis...
September 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28878690/regulation-of-pulmonary-vascular-smooth-muscle-contractility-in-pulmonary-arterial-hypertension-implications-for-therapy
#8
REVIEW
Melissa A Lyle, Jonathan P Davis, Frank V Brozovich
There are two primary components that produce pulmonary arterial hypertension (PAH); aberrant structural changes (smooth muscle cell proliferation, smooth muscle cell hypertrophy, and the deposition of matrix proteins within the media of pulmonary arterial vessels), and excess vasoconstriction. However, in PAH, the target and aim of all current therapeutic agents is to reduce the contractility of the pulmonary vasculature; prostaglandins, phosphodiesterase inhibitors, guanylate cyclase stimulators, endothelin antagonists, NO inhalation and Rho kinase inhibitors all influence signaling pathways in the pulmonary vascular smooth muscle to decrease vasoconstriction, and hence, pulmonary vascular resistance (PVR)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28876118/-effects-of-complement-c5a-inhibitor-therapy-in-animal-models-of-non-occlusive-mesenteric-ischemia
#9
Miklós Nógrády, Gabriella Varga, Szilárd Szűcs, József Kaszaki, Mihály Boros, Dániel Érces
INTRODUCTION: Non-occlusive mesenteric ischemia (NOMI) develops without anatomical causes. Early diagnosis is challenging and treatments are of questionable effectiveness. We investigated the role of complement activation in the pathophysiology of NOMI in animal models through the inhibition of complement C5a. MATERIALS AND METHODS: 60-min partial aortic occlusion (PAO; abdominal aorta, proximal to celiac trunk; mean arterial pressure: 30-40 mmHg) was established in Sprague-Dawley rats (n = 28) and 60-min cardiac tamponade in minipigs (n = 19; mean arterial pressure: 40-50 mmHg) to observe short- and long-term circulatory and inflammatory consequences of NOMI...
September 2017: Magyar Sebészet
https://www.readbyqxmd.com/read/28871941/-elevated-expression-of-endothelin-2-in-lung-tissues-of-asthmatic-rats-after-exposed-to-cigarette-smoke-and-its-mechanism
#10
Fangfang Han, Shuyang Zhu, Bi Chen, Jingjing Li
Objective To study the effect of cigarette smoke exposure on the expression of endothelin 2 (ET-2) in bronchial epithelium of asthmatic rats. Methods Asthma models were established through intraperitoneal injection of 1 mL chicken ovalbumin (OVA)/Al(OH)3 mixture (asthma model group, n=6); based on the asthma models, exposure to smoking gas lasted four weeks with 10 cigarettes per day (smoke-exposed asthma group, n=6); based on the smoke-exposed asthma models, the rats were treated with intraperitoneal injection of dexamethasone 2 mg/(kg...
August 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28865353/mechanisms-involved-in-facial-heat-hyperalgesia-induced-by-endothelin-1-in-female-rats
#11
Rafael Fernandes de Souza, Luana Lechenakoski de Oliveira, Carina Fernanda Mattedi Nones, Renata Cristiane Dos Reis, Erika Ivanna Araya, Caroline Machado Kopruszinski, Giles Alexander Rae, Juliana Geremias Chichorro
OBJECTIVE: Pronociceptive responses to endothelins in the trigeminal system seem to be mediated by ETA and ETB receptors, which have been shown to be expressed in neurons of the trigeminal ganglion of humans and rats. The present study aimed to evaluate the ability of endothelin-1 (ET-1) to induce facial heat hyperalgesia in female rats, the contribution of ETA and ETB receptors to this response, as well as the mechanisms underlying heat hyperalgesia induced by ET-1. DESIGN: ET-1 (100pmol/50μL) was injected into the upper lip and heat hyperalgesia was evaluated for up to 6h...
August 30, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28855187/inhibition-of-smooth-muscle-contraction-and-arf-6-activity-by-the-inhibitor-for-cytohesin-gefs-secinh3-in-the-human-prostate
#12
Annika Herlemann, Patrick Keller, Melanie Schott, Alexander Tamalunas, Anna Ciotkowska, Beata Rutz, Yiming Wang, Qingfeng Yu, Raphaela Waidelich, Frank Strittmatter, Christian G Stief, Christian Gratzke, Martin Hennenberg
Prostate smooth muscle contraction is critical for etiology and treatment of male lower urinary tract symptoms (LUTS), and is promoted by small monomeric GTPases (RhoA, Rac). GTPases may be activated by guanosine nucleotide exchange factors (GEFs). GEFs of the cytohesin family may indirectly activate Rac, or ADP ribosolyation factor (ARF) GTPases directly. Here we investigated the expression of cytohesin family GEFs, and effects of the cytohesin inhibitor secinH3 on smooth muscle contraction and GTPase activities in human prostate tissues...
August 30, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28850965/-how-to-retard-progression-of-chronic-kidney-disease
#13
Markus P Schneider, Karl F Hilgers
End stage chronic kidney disease (CKD) requiring renal replacement therapy is related to poor quality of life and high mortality. Thus, slowing the progression of CKD is an important purpose of therapy. Some general therapeutic approaches aim to slow the decline of renal function and they can be applied in all patients with CKD - irrespective of the underlying cause of CKD. A key intervention is lowering blood pressure (target: ≤ 140/90 mmHg, and in patients with albuminuria ≤ 130/80 mmHg). Inhibitors of the renin angiotensin system preferentially should be used in case of albuminuria, depending on the diabetic status and the level of albuminuria: in diabetics with albuminuria ≥ 30 mg/d, in non-diabetics with albuminuria > 300 mg/d...
September 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28848152/effect-of-the-diabetic-environment-on-the-expression-of-mirnas-in-endothelial-cells-mir-149-5p-restoration-ameliorates-the-high-glucose-induced-expression-of-tnf-%C3%AE-and-er-stress-markers
#14
Jing Yuan, Minghao Chen, Qingyun Xu, Jianxin Liang, Ruixue Chen, Ya Xiao, Meixia Fang, Liguo Chen
BACKGROUND/AIMS: This study aimed to screen microRNAs and their corresponding target genes that are associated with vascular injury in type two diabetes mellitus (T2DM), investigate the effects of differentially expressed miRNAs and their target genes on high glucose-induced vascular injury and establish the mechanism underlying these effects. METHODS: A high-throughput digital gene expression (DGE) sequencing was performed to sequence microRNAs (miRNAs) and messenger RNAs (mRNAs) and determine their differential expression in human umbilical vein endothelial cells (HUVECs) incubated with serum samples from patients with T2DM and healthy volunteers...
August 28, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28835854/retinal-and-choroidal-angiogenesis-a-review-of-new-targets
#15
REVIEW
Thiago Cabral, Luiz Guilherme M Mello, Luiz H Lima, Júlia Polido, Caio V Regatieri, Rubens Belfort, Vinit B Mahajan
Retinal and choroidal neovascularization are a major cause of significant visual impairment, worldwide. Understanding the various factors involved in the accompanying physiopathology is vital for development of novel treatments, and most important, for preserving patient vision. The intraocular use of anti-vascular endothelial growth factor therapeutics has improved management of the retinal and choroidal neovascularization but some patients do not respond, suggesting other vascular mediators may also contribute to ocular angiogenesis...
2017: International Journal of Retina and Vitreous
https://www.readbyqxmd.com/read/28831752/longitudinal-assessment-of-the-effect-of-atrasentan-on-thoracic-bioimpedance-in-diabetic-nephropathy-a-randomized-double-blind-placebo-controlled-trial
#16
David J Webb, Blai Coll, Hiddo J L Heerspink, Dennis Andress, Yili Pritchett, John J Brennan, Mark Houser, Ricardo Correa-Rotter, Donald Kohan, Hirofumi Makino, Vlado Perkovic, Giuseppe Remuzzi, Sheldon W Tobe, Robert Toto, Robert Busch, Pablo Pergola, Hans-Henrik Parving, Dick de Zeeuw
BACKGROUND: Fluid retention is a common adverse event in patients who receive endothelin (ET) receptor antagonist therapy, including the highly selective ETA receptor antagonist, atrasentan. OBJECTIVE: We performed longitudinal assessments of thoracic bioimpedance in patients with type 2 diabetes mellitus and nephropathy to determine whether a decrease in bioimpedance accurately reflected fluid retention during treatment with atrasentan. STUDY DESIGN: We conducted a randomized, double-blind, placebo-controlled study in 48 patients with type 2 diabetes mellitus and nephropathy who were receiving stable doses of renin angiotensin system inhibitors and diuretics...
August 22, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28830211/rhodiola-crenulata-attenuates-high-glucose-induced-endothelial-dysfunction-in-human-umbilical-vein-endothelial-cells
#17
Li-Yen Huang, I-Chuan Yen, Wei-Cheng Tsai, Blerina Ahmetaj-Shala, Tsu-Chung Chang, Chien-Sung Tsai, Shih-Yu Lee
Rhodiola crenulata root extract (RCE), a traditional Chinese medicine, has been shown to regulate glucose and lipid metabolism via the AMPK pathway in high glucose (HG) conditions. However, the effect of RCE on HG-induced endothelial dysfunction remains unclear. The present study was designed to examine the effects and mechanisms of RCE against hyperglycemic insult in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were pretreated with or without RCE and then exposed to 33[Formula: see text]mM HG medium...
August 22, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28820947/dysregulated-mitogen-activated-protein-kinase-and-matrix-metalloproteinase-in-ethanol-induced-cavernosal-dysfunction
#18
Jaqueline Jóice Muniz, Leticia Nogueira Leite, Riccardo Lacchini, Jose E Tanus-Santos, Carlos Renato Tirapelli
We evaluated the effects of ethanol consumption on the mitogen-activated protein kinases (MAPK) and metalloproteinases (MMP) pathways in the rat cavernosal smooth muscle (CSM). Male Wistar rats were treated with ethanol (20% vol./vol.) for six weeks. Quantitative real-time polymerase chain reaction experiments showed that ethanol consumption did not alter mRNA levels of p38MAPK, SAPK/JNK, ERK1/2, MMP-2 or MMP-9 in the rat CSM. Western immunoblotting experiments revealed decreased protein expression of p38MAPK and phosphorylation of SAPK/JNK in the CSM from ethanol-treated rats...
August 18, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28819824/-update-pulmonary-arterial-hypertension-definitions-diagnosis-therapy
#19
N Sommer, M J Richter, K Tello, F Grimminger, W Seeger, H A Ghofrani, H Gall
The term pulmonary arterial hypertension comprises a group of pulmonary vascular diseases of different etiologies that are characterized by similar precapillary vascular remodeling processes and result in exertional dyspnea and right heart insufficiency. The specific pharmacological treatment approach considers the risk of mortality and phenotypical properties and includes treatment with phosphodiesterase type 5 inhibitors, endothelin receptor antagonists and prostanoids, as well as with more novel substances, such as a soluble guanylyl cyclase stimulator and an oral prostacyclin receptor agonist...
August 17, 2017: Der Internist
https://www.readbyqxmd.com/read/28808570/nitric-oxide-cyclic-gmp-pathway-mediates-the-endothelin-1-upregulation-of-adiponectin-expression-in-rat-cardiomyocytes
#20
Bingyan Guo, Yongjun Li, Xin Jin, Suyun Liu, Chenglong Miao
Endothelin-1 (ET-1) serves an important role in the development of cardiac dysfunction and heart failure. ET-1 and angiotensin II (AngII) comprise a mutually reciprocal signalling network in the myocardium and serve similar or additive roles in the development of heart failure. Our previous study previously demonstrated that AngII upregulated the expression of APN in cardiomyocytes through an AngII receptor type 2/nitric oxide (NO)/cyclic GMP(cGMP)-dependent pathway. The purpose of the present study was to determine the effects of ET-1 and the additive effects of ET-1 and AngII on the gene expression and secretion of APN, and the underlying mechanisms involved...
September 2017: Biomedical Reports
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