Vol 2-5 Commentary

Commentary: Distinct Domains in The Matricellular Protein, Lonely Heart, Are Crucial for Cardiac Extracellular Matrix Formation and Heart Function in Drosophila

Yanina Post, Achim Paululat*

University of Osnabrueck, Faculty of Biology & Chemistry, Zoology and Developmental Biology, Barbarastraße 11, 49076 Osnabrueck, Germany

It is well known that cardiovascular diseases are becoming the number one cause of mortality in developed countries1. Minimal differences in a wide range of biological pathways can lead to organ malfunction or failure. In addition to the heart itself, its surroundings are also crucial for proper organ integrity and functionality. Changes in extracellular matrix (ECM) composition, such as a higher amount of incorporated collagens, can result in cardiac hypertrophy2 or hypertension-related diastolic dysfunction3 by stiffening the surrounding matrix and constricting the embedded organ. Similar observations have been made while studying the heart of the fruit fly, Drosophila melanogaster. In this model organism, altered amounts of ECM components, including Laminin or Collagen IV (Viking), cause impaired cardiac function4. This demonstrates the notable relevance of an organ-specific ECM composition that provides the correct balance of stiffness and elasticity, both in vertebrates and invertebrates. In our recent study we were able to unravel the function of several protein domains belonging to the ADAMTS-like protein Lonely heart5. Furthermore, we analysed its interaction with the Collagen IV-like protein Pericardin and described new interactions within the extracellular matrix that led to a more detailed model of the whole network. In addition, we investigated the impact of altered Pericardin levels on physiological aspects, including locomotion and heart beating parameters, and strengthened the hypothesis that ECM composition is crucial for proper organ functionality. Here we summarize our approaches and comment on additional observations, possible follow-up analyses and restrictions as well as advantages. Moreover, we discuss possible additional roles of ADAMTS-like proteins within an extracellular matrix.

DOI: 10.29245/2578-3025/2018/5.1143 View / Download Pdf
Vol 2-5 Mini Review

Protective Effects of Angiotensin-Converting-Enzyme-2 on Renal Dysfunction in Obstructive Jaundice

Mo Chen , Hongqian Wang , Erliang Kong , Jinmin Zhang , Weifeng Yu , Feixiang Wu*

Department of Anesthesiology & Intensive Care, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China

Acute renal failure occurring in patients with obstructive jaundice after surgery is still a serious clinical complication. Renin-angiotensin-aldosterone system (RAAS) plays a key role in the progression of kidney disease. Previous studies have demonstrated that angiotensin-converting-enzyme-2 (ACE2), a component of the RAAS system, acts as a local regulator for renal protection, and has a beneficial effect on renal fibrosis. This review will summarize the role of ACE2 and the protective effects on renal dysfunction in obstructive jaundice.

DOI: 10.29245/2578-3025/2018/5.1146 View / Download Pdf
Vol 2-5 Mini Review

Characterization of Coronary Plaque in Psoriasis and the Impact of Current Therapies

Ashlee L Culver1, Annika S Silfvast-Kaiser2, Alan Menter1,2*

1Texas A&M Health Science Center College of Medicine, TX

2Division of Dermatology, Baylor University Medical Center, Dallas, TX

Psoriasis is a systemic inflammatory disease which contributes to an increased risk for cardiovascular disease, specifically coronary artery disease. Patients with psoriasis tend to have greater total coronary plaque burden and more high risk plaque than healthy controls. This likely contributes to the higher rate of myocardial infarction and 4-5 year reduction in lifespan observed in our psoriasis population. With biologic therapy and improvement in PASI scores, total plaque burden and noncalcified coronary plaque decreases as well. Specifically, ustekinumab decreases intima-media thickness and reduces vascular inflammation. Likewise, TNF-α inhibitors decrease vascular inflammation and reduce cardiovascular events in both sexes, and reduce coronary plaque formation in men with psoriasis. This may be due to elevation in glycoprotein acetylation, which is associated with cardiovascular events and elevated in psoriasis. This elevation has also been shown to decrease with adalimumab usage. Despite all of the knowledge gained on this topic, the incidence of myocardial infarction in psoriasis patients currently remains unchanged when compared to prior years. Consequently, we emphasize the need for further research on the unique pathogenesis of psoriatic coronary plaque formation as well as the effect biologic agents have on this coronary plaque in order to improve the wellbeing of this patient population.

DOI: 10.29245/2578-3025/2018/5.1149 View / Download Pdf
Vol 2-5 Review Article

Pathogenesis Of Portal Vein Thrombosis In Liver Cirrhosis: The Role of the ADAMTS13/VWF Unbalance

Monica Sacco1*, Stefano Lancellotti1*, Maria Basso1, Raimondo De Cristofaro1,2*

1Servizio Malattie Emorragiche e Trombotiche, Fondazione Policlinico Universitario “A. Gemelli”, IRCCS, Italy

2Istituto di Medicina Interna e Geriatria, Università Cattolica S. Cuore, Roma, Italy

Increasing evidence shows a potential role of ADAMTS13 deficiency as a risk factor for the high prevalence of portal vein thrombosis (PVT) in cirrhotic patients. This deficiency, due to myofibroblastic transformation of hepatic stellate cells (HSCs), the source of ADAMTS13, is responsible for the prevalence of ultra large molecular weight multimers of von Willebrand factor (UL-VWF) in the hepatic microcirculation. This phenomenon would favor the pro-haemostatic function of VWF, which, together with an elevation of coagulation FVIII, which is associated to VWF, could sustain microcirculatory thrombosis in the liver. These phenomena, triggering an increase of the intra-hepatic pressure, would cause a slowdown of the portal flow, favoring the occurrence of PVT. Although this scenario is justified by retrospective observational clinical studies, it will be mandatory to clarify the ADAMTS13 expression in HSCs associated with the activity of plasma ADAMTS13 in different stage of liver diseases. Hence, a prospective clinical trial (ClinicalTrials.gov Identifier: NCT03322696) is ongoing to unravel the linkage between all the actors involved in the complex phenomenon of PVT occurring in cirrhosis.

DOI: 10.29245/2578-3025/2018/5.1150 View / Download Pdf
Vol 2-5 Commentary

Commentary: "Single Center Experience with the AngioVac Aspiration System."

Jason Salsamendi, Yi Shuen Chang*

Department of Vascular and Interventional Radiology, University of Miami Miller School of Medicine/Jackson Memorial Hospital, 1611 NW 12th Ave. WW-279, Miami, FL, 33136, USA

DOI: 10.29245/2578-3025/2018/5.1152 View / Download Pdf
Vol 2-5 Commentary

Commentary: Predicting Outcomes in Patients with Asymptomatic Moderate to Severe Aortic Stenosis

Robert C Bahler*, Neal V Dawson

Case Western Reserve University School of Medicine at MetroHealth Medical Center, Cleveland, Ohio, United States of America

Outcomes in patients with moderate to severe aortic stenosis (AS) from a community hospital cohort are similar those reported from tertiary institutions. Echocardiographic measures of the severity of obstruction are key variables in predicting outcomes. Additional variables that are not direct measures of AS severity are associated with adverse events. A reduced left ventricular (LV) ejection fraction forecasts a less favorable outcome yet most asymptomatic patients have preserved LV ejection fractions. Consequently, other measures of LV systolic function associated with adverse outcomes are important; namely, reduced LV longitudinal shortening and increased LV mass. Diastolic function can be compromised in AS indicated by either elevated E/e´ or left atrial enlargement; both are associated with unfavorable outcomes. Electrocardiographic evidence of LV strain reflects LV mid-wall fibrosis and identifies patients with adverse outcomes. Biomarkers including elevated values of high sensitivity troponin I and BNP contribute to models predicting outcomes. Prediction models help identify asymptomatic patients with quite unfavorable prognoses who may benefit from early aortic valve replacement.

DOI: 10.29245/2578-3025/2018/5.1157 View / Download Pdf
Vol 2-5 Review Article

Review Article: The Effect of Performing a Paracentesis on Hospital Outcomes

Lindsay A Sobotka*, Khalid Mumtaz#

Department of Gastroenterology, Hepatology and Nutrition, The Ohio State Wexner Medical Center, USA

Decompensated cirrhosis with ascites results in high health care expenditures, 30 day readmission, morbidity, and mortality. Paracentesis is indicated in patients with cirrhosis and ascites to rule out spontaneous bacterial peritonitis and for symptomatic control. Performing at least a diagnostic paracentesis has been proved to reduce inpatient mortality; however, the procedure was also associated with longer length of stay, higher costs during hospitalization and increased risk of 30-day readmission. In summary, diagnostic paracentesis is crucial to rule out infection, but other interventions should be utilized to control ascites, as worse hospital outcomes as likely associated with a large volume paracentesis.

DOI: 10.29245/2578-3025/2018/5.1153 View / Download Pdf
Vol 2-5 Review Article

Venous Thrombophilia, Platelet von Willebrand Factor Mediated Arteriolar Microvascular Thrombosis in JAK2V617F Mutated Thrombocythemia and Acquired ADAMTS13 Deficiency as Causes of Intrahepatic Obstructive Microvascular Liver Diseases in Budd-Chiari Syndrome and Splanchnic Vein Thrombosis

Jan Jacques Michiels1,3*, Petr Dulicek2, Zwi Berneman1, Alain Gadisseur1, Wilfried Schroyens1

1Departments of Hematology and Coagulation Research, University Hospital Antwerp, Belgium

2Fourth Department of Internal Medicine–Hematology, University Hospital in Hradec Kralove and Charles University Prague, Faculty of Medicine in Hradec Kralove and Prague, Czech Republic on behave of the Central European Vascular Forum: CEVF

3Blood, Coagulation and Cardiovascular Medicine Research Center and International Collaboration and Academic Research on Myeloproliferative Neoplasms: ICAR.MPN, Goodheart Institute & Foundation in Nature Medicine & Health, Rotterdam, The Netherlands

Congenital venous thrombophilia is associated with increased risk of venous thrombosis at adolescent and adult age, with recurrent abortions and fetal loss in females, and less frequently with splanchnic vein thrombosis, but not with arteriolar microvascular circulation disturbances. Based on original observations in view of the literature on thrombocythemia in patients with essential thrombocythemia (ET) and polycythemia vera (PV), both ET and PV are associated with increased risk of platelet-von Willebrand factor (VWF) mediated arteriolar microvascular circulation disturbances at adult age, with recurrent abortions and fetal loss in females, and less frequently with splanchnic vein thrombosis, but not with venous thromboembolism.

The high incidences of congenital venous thrombophilic factors including antithrombin III, protein C and S, factor V Leiden and the prothrombin G20210A mutation, acquired lupus anticoagulant as well as the presence of the JAK2V617F mutation indicative for thrombocythemia in trilinear myeloproliferative disease (MPD) are described as the underlying hypercoagulable states in patients with Budd-Chiari syndrome (BCS) and splanchnic vein thrombosis (SVT). In this editorial we propose the novel concept of coagulation and/or platelet mediated microvascular liver pathology is the primary event for the development of BCS, splanchnic vein thrombosis, and portal hypertension with portal and oesophageal varicosal veins as a serious complication in patients with congenital thrombophilia and/or JAK2V617F mutated sticky platelets in clonal ET and PV. Clinical and liver pathology observations are in line with a two hit hypothesis of coagulation- and/or platelet-mediated thrombosis in the liver microcirculation as the underlying etiology of BCS and splanchnic vein thrombosis in patients with congenital venous thrombophilia and/or an acquired JAK2V617F mutated thrombocythemia in ET and PV patients. Severe ADAMTS13 deficiency in advanced liver cirrhosis is related to the severity of liver cell insufficiency due to the combined ADAMTS13 synthesis defect and autoantibodies against ADAMTS13 thereby explaining the more pronounced ADAMTS13 deficiency as compared to the degree of AT III synthesis deficiency in advanced liver cirrhosis. An imbalance between the severely decreased ADAMTS13:AC level and its substrate may indeed reflect the predisposing state for platelet thrombi in the liver microcirculation in patients with advanced liver cirrhosis similar on op of congenital venous thrombophilia and platelet-VWF mediated arteriolar microvascular thrombosis in JAK2V617F mutated thrombocythemia as etiological risk factors of intrahepatic microvascular obstructive diseases in BCS followed by splanchnic vein thrombosis.

DOI: 10.29245/2578-3025/2018/5.1154 View / Download Pdf