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https://www.readbyqxmd.com/read/28796163/hypertension-caused-by-lenvatinib-and-everolimus-in-the-treatment-of-metastatic-renal-cell-carcinoma
#1
REVIEW
Mathias Alrø Fichtner Bendtsen, Daniela Grimm, Johann Bauer, Markus Wehland, Petra Wise, Nils E Magnusson, Manfred Infanger, Marcus Krüger
Multikinase inhibitors (MKI) and mammalian target of rapamycin (mTOR) inhibitors prolong progression-free (PFS) and overall survival (OS) in the treatment of metastatic renal cell carcinoma (mRCC) by reducing angiogenesis and tumor growth. In this regard, the MKI lenvatinib and the mTOR inhibitor everolimus proved effective when applied alone, but more effective when they were administered combined. Recently, both drugs were included in clinical trials, resulting in international clinical guidelines for the treatment of mRCC...
August 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28743805/ephrinb2-regulates-cardiac-fibrosis-through-modulating-the-interaction-of-stat3-and-tgf-%C3%AE-smad3-signaling
#2
Sheng-An Su, Du Yang, Yue Wu, Yao Xie, Wei Zhu, Zhejun Cai, Jian Shen, Zurong Fu, Yaping Wang, Liangliang Jia, Yidong Wang, Jian'an Wang, Meixiang Xiang
Rationale: Cardiac fibrosis is a common feature in left ventricular remodeling that leads to heart failure, regardless of the etiology. Erythropoietin-producing hepatoma interactor B2 (EphrinB2), a pivotal bidirectional signaling molecule ubiquitously expressed in mammals, is crucial in angiogenesis during development and disease progression. Recently, EphrinB2 was reported to protect kidneys from injury-induced fibrogenesis. However, its role in cardiac fibrosis remains to be clarified. Objective: We sought to determine the role of EphrinB2 in cardiac fibrosis and the underlying mechanisms during the pathological remodeling process...
July 25, 2017: Circulation Research
https://www.readbyqxmd.com/read/28737214/decline-in-cellular-function-of-aged-mouse-c-kit-cardiac-progenitor-cells
#3
Alessandra Castaldi, Ramsinh Mansinh Dodia, Amabel M Orogo, Cristina M Zambrano, Rita H Najor, Åsa B Gustafsson, Joan Heller Brown, Nicole H Purcell
Therapeutic use of c-kit(+) cardiac progenitor cells (CPCs) is being evaluated for regenerative therapy in older patients with ischemic heart failure. Our understanding of the biology of these CPCs has however, largely come from studies of young cells and animal models. In the present study we examined characteristics of CPCs isolated from young (3 months) and aged (24 month) mice that could underlie the diverse outcomes reported for CPC-based therapeutics. We observed morphological differences and altered senescence indicated by increased senescence associated markers β-galactosidase and p16 mRNA in aged CPCs...
July 24, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28724653/haplodeficiency-of-ataxia-telangiectasia-mutated-accelerates-heart-failure-after-myocardial-infarction
#4
Lixin Jia, Wenmei Zhang, Youcai Ma, Boya Chen, Yan Liu, Chunmei Piao, Yuan Wang, Min Yang, Tingting Liu, Junmeng Zhang, Taotao Li, Shaoping Nie, Jie Du
BACKGROUND: Cell senescence is involved in the process of organ damage and repair; however, the underlying molecular mechanism needs to be further explored. METHODS AND RESULTS: Senescence-related genes (ie, p21, p53, and ataxia telangiectasia mutated [ATM]) were shown to be elevated after myocardial infarction (MI) in both mouse and human hearts. Ten- to 12-week-old male wild-type littermates (ATM(+/+)) and ATM heterozygous mice (ATM(+/-)) were subjected to MI...
July 19, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28688145/therapeutic-concentrations-of-digitoxin-inhibit-endothelial-focal-adhesion-kinase-and-angiogenesis-induced-by-diverse-growth-factors
#5
Annalisa Trenti, Elisabetta Zulato, Lorenza Pasqualini, Stefano Indraccolo, Chiara Bolego, Lucia Trevisi
BACKGROUND AND PURPOSE: Cardiac glycosides are Na(+) /K(+) -ATPases inhibitors used to treat congestive heart failure and cardiac arrhythmias. Epidemiological studies indicate that patients on digitalis therapy are more protected from cancer. Evidence of a selective cytotoxicity against cancer cells has suggested their potential use as anticancer drugs. The effect on angiogenesis of clinically used cardiac glycosides has not been extensively explored. EXPERIMENTAL APPROACH: We studied the effect of digoxin, digitoxin and ouabain on early events of the angiogenic process in human umbilical vein endothelial cells (HUVEC)...
July 8, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28683969/impact-of-oxidative-stress-on-the-heart%C3%A2-and-vasculature-part-2-of-a-3-part-series
#6
REVIEW
Thomas Münzel, Giovanni G Camici, Christoph Maack, Nicole R Bonetti, Valentin Fuster, Jason C Kovacic
Vascular disease and heart failure impart an enormous burden in terms of global morbidity and mortality. Although there are many different causes of cardiac and vascular disease, most causes share an important pathological mechanism: oxidative stress. In the failing heart, oxidative stress occurs in the myocardium and correlates with left ventricular dysfunction. Reactive oxygen species (ROS) negatively affect myocardial calcium handling, cause arrhythmia, and contribute to cardiac remodeling by inducing hypertrophic signaling, apoptosis, and necrosis...
July 11, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28650928/circulating-exosomes-isolated-from-septic-mice-induce-cardiovascular-hyperpermeability-through-promoting-podosome-cluster-formation
#7
Xingjiang Mu, Xiaohong Wang, Wei Huang, Rui-Tao Wang, Kobina Essandoh, Yutian Li, Amanda M Pugh, Jiangtong Peng, Shan Deng, Yigang Wang, Charles C Caldwell, Tianqing Peng, Kai-Jiang Yu, Guo-Chang Fan
Septic shock increases vascular permeability, leading to multiple organ failure including cardiac dysfunction, a major contributor to septic death. Podosome, an actin-based dynamic membrane structure, plays critical roles in extracellular matrix degradation and angiogenesis. However, whether podosome contributes to endothelial barrier dysfunction during septic shock remains unknown. In this study, we found that the endothelial hyperpermeability, stimulated by PMA and thrombin, was accompanied by increased formation of podosome clusters at the cell periphery, indicating a positive correlation between podosome clusters and endothelial leakage...
June 23, 2017: Shock
https://www.readbyqxmd.com/read/28639369/a-network-analysis-to-compare-biomarker-profiles-in-patients-with-and-without-diabetes-mellitus-in-acute-heart-failure
#8
Abhinav Sharma, Biniyam G Demissei, Jasper Tromp, Hans L Hillege, John G Cleland, Christopher M O'Connor, Marco Metra, Piotr Ponikowski, John R Teerlink, Beth A Davison, Michael M Givertz, Daniel M Bloomfield, Howard Dittrich, Dirk J van Veldhuisen, Gad Cotter, Justin A Ezekowitz, Mohsin A F Khan, Adriaan A Voors
AIMS: It is unclear whether distinct pathophysiological processes are present among patients with acute heart failure (AHF), with and without diabetes. Network analysis of biomarkers may identify correlative associations that reflect different pathophysiological pathways. METHODS AND RESULTS: We analysed a panel of 48 circulating biomarkers measured within 24 h of admission for AHF in a subset of patients enrolled in the PROTECT trial. In patients with and without diabetes, we performed a network analysis to identify correlations between measured biomarkers...
June 21, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28637870/cardiac-myocyte-p38%C3%AE-kinase-regulates-angiogenesis-via-myocyte-endothelial-cell-cross-talk-during-stress-induced-remodeling-in-the-heart
#9
Beth A Rose, Tomohiro Yokota, Vishnu Chintalgattu, Shuxun Ren, Luisa Iruela-Arispe, Aarif Y Khakoo, Susumu Minamisawa, Yibin Wang
Stress-induced p38 mitogen-activated protein kinase (MAPK) activity is implicated in pathological remodeling in the heart. For example, constitutive p38 MAPK activation in cardiomyocytes induces pathological features, including myocyte hypertrophy, apoptosis, contractile dysfunction, and fetal gene expression. However, the physiological function of cardiomyocyte p38 MAPK activity in beneficial compensatory vascular remodeling is unclear. This report investigated the functional role and the underlying mechanisms of cardiomyocyte p38 MAPK activity in cardiac remodeling induced by chronic stress...
August 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28624483/biomarker-profiles-of-acute%C3%A2-heart%C3%A2-failure%C3%A2-patients-with-a%C3%A2-mid-range-ejection%C3%A2-fraction
#10
Jasper Tromp, Mohsin A F Khan, Robert J Mentz, Christopher M O'Connor, Marco Metra, Howard C Dittrich, Piotr Ponikowski, John R Teerlink, Gad Cotter, Beth Davison, John G F Cleland, Michael M Givertz, Daniel M Bloomfield, Dirk J Van Veldhuisen, Hans L Hillege, Adriaan A Voors, Peter van der Meer
OBJECTIVES: In this study, the authors used biomarker profiles to characterize differences between patients with acute heart failure with a midrange ejection fraction (HFmrEF) and compare them with patients with a reduced (heart failure with a reduced ejection fraction [HFrEF]) and preserved (heart failure with a preserved ejection fraction [HFpEF]) ejection fraction. BACKGROUND: Limited data are available on biomarker profiles in acute HFmrEF. METHODS: A panel of 37 biomarkers from different pathophysiological domains (e...
July 2017: JACC. Heart Failure
https://www.readbyqxmd.com/read/28603431/hereditary-hemorrhagic-telangiectasia-and-pregnancy-potential-adverse-events-and-pregnancy-outcomes
#11
REVIEW
Omar Bari, Philip R Cohen
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant condition with a prevalence of ~1 in 5,000 individuals. The pathophysiology of this condition centers on the lack of capillary beds between arterioles and venules, leading to direct contact between these vessels. This results in telangiectases on characteristic locations such as the face, fingers, mouth, and nasal mucosa. Visceral arteriovenous malformations (AVMs) are also observed in many patients, and these are most commonly seen in the brain, gastrointestinal tract, and lungs...
2017: International Journal of Women's Health
https://www.readbyqxmd.com/read/28565779/expression-of-integrin-linked-kinase-improves-cardiac-function-in-a-swine-model-of-myocardial-infarction
#12
Wen Lu, Jun Xie, Rong Gu, Biao Xu
Previous studies have described the beneficial effects of overexpressing integrin-linked kinase (ILK) after myocardial infarction (MI) in small animal models. However, the effects of ILK in pre-clinical large animals are not known. To move closer to clinical translation, we examined the effects of ILK gene transfer in a swine model of ischemic heart disease. Swine received percutaneous intracoronary injections of adenoviral vector expressing ILK (n=10) or empty ad-null (n=10) in the left anterior descending coronary artery (LAD) following LAD occlusion...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28553113/methotrexate-carried-in-lipid-core-nanoparticles-reduces-myocardial-infarction-size-and-improves-cardiac-function-in-rats
#13
Raul C Maranhão, Maria C Guido, Aline D de Lima, Elaine R Tavares, Alyne F Marques, Marcelo D Tavares de Melo, Jose C Nicolau, Vera Mc Salemi, Roberto Kalil-Filho
PURPOSE: Acute myocardial infarction (MI) is accompanied by myocardial inflammation, fibrosis, and ventricular remodeling that, when excessive or not properly regulated, may lead to heart failure. Previously, lipid core nanoparticles (LDE) used as carriers of the anti-inflammatory drug methotrexate (MTX) produced an 80-fold increase in the cell uptake of MTX. LDE-MTX treatment reduced vessel inflammation and atheromatous lesions induced in rabbits by cholesterol feeding. The aim of the study was to investigate the effects of LDE-MTX on rats with MI, compared with commercial MTX treatment...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28552862/imbalanced-angiogenesis-in-peripartum-cardiomyopathy%C3%A3-diagnostic-value-of-placenta-growth-factor
#14
Alexandre Mebazaa, Marie-France Seronde, Etienne Gayat, Kemi Tibazarwa, Dilly O C Anumba, Najla Akrout, Malha Sadoune, Jamela Sarb, Mattia Arrigo, Justina Motiejunaite, Said Laribi, Matthieu Legrand, Lydia Deschamps, Loubina Fazal, Lila Bouadma, Corinne Collet, Philippe Manivet, Alain Cohen Solal, Jean-Marie Launay, Jane-Lise Samuel, Karen Sliwa
BACKGROUND: Concentrations of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) are altered in peripartum cardiomyopathy (PPCM). In this study we investigated changes in the angiogenesis balance in PPCM.Methods and Results:Plasma concentrations of sFlt-1 and the pro-angiogenic placenta growth factor (PlGF) were determined in patients with PPCM during the post-partum phase (n=83), in healthy women at delivery (n=30), and in patients with acute heart failure (AHF; n=65)...
May 27, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28536660/sorafenib-associated-heart-failure-complicated-by-cardiogenic-shock-after-treatment-of-advanced-stage-hepatocellular-carcinoma-a-clinical-case-discussion
#15
Candace Wu, Kamal Shemisa
Background. Sorafenib, an oral tyrosine kinase inhibitor (TKI), targets multiple tyrosine kinase receptors (TKRs) involved in angiogenesis and tumor growth. Studies suggest that inhibition of TKR impacts cardiomyocyte survival. Inhibition of VEGF signaling interrupts angiogenesis and is associated with the development of hypertension and compensatory hypertrophy. Compensated hypertrophy ultimately leads to heart failure. Case Description. A 76-year-old man with a past medical history of systolic heart failure due to ischemic cardiomyopathy and stage IIIC hepatocellular carcinoma (HCC) presented with symptoms of decompensated heart failure...
2017: Case Reports in Cardiology
https://www.readbyqxmd.com/read/28474327/pet-imaging-in-heart-failure-the-role-of-new-tracers
#16
REVIEW
Antti Saraste, Juhani Knuuti
Positron emission tomography (PET) myocardial perfusion imaging is being increasingly used for the detection of coronary artery disease. In the presence of significant left ventricle dysfunction, the assessment of myocardial ischemia and viability by PET plays a role in the identification of patients who may benefit from revascularization. In addition to these, new PET tracers may play a role in the assessment of underlying pathophysiology and therapeutic options in heart failure. Studies have shown the ability of sympathetic innervation imaging to assess the risk of cardiac death, arrhythmia, and disease progression...
May 5, 2017: Heart Failure Reviews
https://www.readbyqxmd.com/read/28453725/serelaxin-treatment-promotes-adaptive-hypertrophy-but-does-not-prevent-heart-failure-in-experimental-peripartum-cardiomyopathy
#17
Justus Nonhoff, Melanie Ricke-Hoch, Mirco Mueller, Britta Stapel, Tobias Pfeffer, Martina Kasten, Michaela Scherr, Constantin von Kaisenberg, Johann Bauersachs, Arash Haghikia, Denise Hilfiker-Kleiner
Aims: Peripartum cardiomyopathy (PPCM) is a systolic left ventricular dysfunction developing in the peripartum phase in previously healthy women. Relaxin-2 is a pregnancy hormone with potential beneficial effects in heart failure patients. We evaluated Relaxin-2 as a potential diagnostic marker and/or a therapeutic agent in PPCM. Methods and results: In healthy peripartum women, serum Relaxin-2 levels (measured by ELISA in the second half of pregnancy) were elevated showing a decreasing trend in the first postpartum week and returned to non-pregnant levels thereafter...
May 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28446517/a-novel-%C3%AE-calcitonin-gene-related-peptide-analogue-protects-against-end-organ-damage-in-experimental-hypertension-cardiac-hypertrophy-and-heart-failure
#18
Aisah A Aubdool, Pratish Thakore, Fulye Argunhan, Sarah-Jane Smillie, Moritz Schnelle, Salil Srivastava, Khadija M Alawi, Elena Wilde, Jennifer Mitchell, Keith Farrell-Dillon, Daniel A Richards, Giuseppe Maltese, Richard C Siow, Manasi Nandi, James E Clark, Ajay M Shah, Anette Sams, Susan D Brain
Background -Research into the therapeutic potential of α-calcitonin gene-related peptide (α-CGRP) has been limited due to its peptide nature and short half-life. Here, we evaluate whether a novel potent and long lasting (t½ ≥ 7h) acylated α-CGRP analogue (αAnalogue) could alleviate and reverse cardiovascular disease in two distinct murine models of hypertension and heart failure in vivoMethods -The ability of the αAnalogue to act selectively via the CGRP pathway was shown in skin using a CGRP receptor antagonist...
April 26, 2017: Circulation
https://www.readbyqxmd.com/read/28395201/syndecan-4-deficiency-accelerates-the-transition-from-compensated-hypertrophy-to-heart-failure-following-pressure-overload
#19
Guannan Li, Jun Xie, Jianzhou Chen, Ran Li, Han Wu, Xinlin Zhang, Qinhua Chen, Rong Gu, Biao Xu
Increasing evidence suggests that a mismatch between angiogenesis and myocardial growth contributes to the transition from adaptive cardiac hypertrophy to heart failure following pressure overload. Syndecan-4 is a transmembrane proteoglycan that binds to growth factors and extracellular matrix proteins and is critical in focal adhesion formation. However, its effects on coronary angiogenesis during pressure overload-induced heart failure have not been studied. Here, we hypothesize that syndecan-4 modulates cardiac remodeling in response to pressure overload through its ability to regulate adaptive angiogenesis...
May 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/28374177/cardiac-complications-of-cancer-therapy-pathophysiology-identification-prevention-treatment-and-future-directions
#20
REVIEW
Diwakar Jain, Raymond R Russell, Ronald G Schwartz, Gurusher S Panjrath, Wilbert Aronow
PURPOSE OF REVIEW: Cardiotoxicity is an important complication of cancer therapy. With a significant improvement in the overall survival and prognosis of patients undergoing cancer therapy, cardiovascular toxicity of cancer therapy has become an important public health issue. Several well-established as well as newer anticancer therapies such as anthracyclines, trastuzumab, and other HER2 receptor blockers, antimetabolites, alkylating agents, tyrosine kinase inhibitors, angiogenesis inhibitors, checkpoint inhibitors, and thoracic irradiation are associated with significant cardiotoxicity...
May 2017: Current Cardiology Reports
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