Volume Articles

Commentary: Effects of lipoprotein apheresis on PCSK9 levels

Ulrich Julius^1*

^*1Lipidology and Center for Extracorporeal Treatment, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Germany

Utilization of ICF in medical rehabilitation in Germany with a focus on cardiac rehabilitation

Tobias-Raphael Wenzel¹, Matthias Morfeld^1,2*

¹Institute for Healthcare research, Intervention, Therapy and Evaluation e.V., Stendal, Germany

^*2University of Applied Sciences Magdeburg-Stendal, Rehabilitation Psychology, Stendal, Germany

In Germany, the International Classification of Functioning, Disability and Health (ICF) is anchored in social law and it provides an important theoretical basis for rehabilitative action. Basically, there is an information deficit regarding the use of the ICF in rehabilitative practice in Germany. From the few publications available it can be concluded that the ICF in the practice of medical rehabilitation in Germany is used differently in nature and extent by social insurance agencies and service providers. There is a need for research to better map, support and develop the utilization of the ICF in the practice of medical rehabilitation in Germany.

Improving HDL Functions - A New Version of The Quest of SANCGREAL?

Alvaro D. B. Bordalo*

*Consultant in Cardiology (ret.), Preoperative Outpatient Clinic (former Head), Cardio-Thoracic Surgery Department, Hospital de Santa Maria, University of Lisbon School of Medicine, Lisbon, Portugal

HDL complex has multiple functions. There is some parallelism between the plasma HDL-cholesterol (HDL-C) concentrations and the HDL complex atheroprotective function, but those values only measure the reverse C-transport. Multiple epidemiological studies have shown that a high HDL-C level is a strong marker of protection against atherosclerotic vascular disease (AVD) development, but in about 10% of patients, there is no correlation between AVD presence or absence and low or high HDL-C values, respectively. Plasma HDL-C concentrations have multiple genetic determinants, but most of the genetic profiles responsible for the association of high HDL-C levels with atheroprotection are not yet identified. A meta-analysis demonstrated that the HDL capacity of C-acceptance from macrophages is inversely associated with AVD prevalence but is independent of HDL-C values. CETP-inhibition therapies, in spite of up to 133% HDL-C increases, failed to improve AVD secondary prevention. As a consequence, the main focus of research has changed and resides now on attempts to improve HDL complex functionality. Elderly AVD-free aortic stenosis patients represent a natural laboratory terrain for use in studies to identify the HDL complex components responsible for successful atheroprotection. However, the reasons why HDL complex, competent for AVD protection for several decades, fails to prevent aortic sclerosis/calcification in the same patients, remain unknown.

Protective Mechanism of Thioredoxin-1 against Atherosclerotic Endothelial Injury Induced by Ox-LDL

Lu Feng¹, Gexin Zhao^2*, Beidong Chen^1*

^*1The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, 100730, China

^*2Technology Center for Genomics & Bioinformatics. Department of Pathology & Laboratory Medicine, David Geffen School of Medicine, University of California, California 90095, USA

Atherosclerosis is a chronic inflammation disease that is initiated by endothelial cell injury. Hyperlipidemia is an independent risk factor for atherosclerosis. Oxidized low-density lipoprotein (ox-LDL) is a major component of hyperlipidemia and contributes to atherosclerosis. Ox-LDL and ox-LDL-related reactive oxygen species (ROS) and inflammation have deleterious effects on vascular endothelial cells. Previous studies have demonstrated that thioredoxin-1 (Trx) is one of the key regulators of intracellular redox, which may play a role in the pathogenesis of atherosclerosis. This review will summarize the protective mechanisms of Trx on endothelial injury induced by ox-LDL.

Commentary: Arrhythmogenic Cardiomyopathy Related DSG2 Mutations Affect Cadherin Binding Kinetics

Volker Walhorn¹, Mareike Dieding¹, Jana Davina Debus², Raimund Kerkhoff¹, Anna Gärtner-Rommel², Hendrik Milting², and Dario Anselmetti¹

¹Experimental Biophysics, Physics Faculty, Bielefeld University, D-33615 Bielefeld, Germany

²Erich & Hanna Klessmann Institute for Cardiovascular Research and Development, Heart and Diabetes Center NRW,University Hospital of the Ruhr-University Bochum, D- 32545 Bad Oeynhausen, Germany

Cadherins are calcium dependent adhesion proteins that bridge the intercellular gap and establish a tight connection to adjacent cells. Desmoglein-2 (DSG2) is a specific cadherin of the cell-cell contact in cardiac desmosomes. Mutations in the DSG2 gene are associated with rare but severe heart muscle diseases such as arrhythmogenic right ventricular cardiomyopathy (ARVC). However, the molecular pathomechanism of many DSG2 mutations is unknown. In our recently published research, we report on the homophilic binding properties of wildtype DSG2 and two mutations thereof. We found that wildtype DSG2 binding kinetics differs significantly from the two analyzed mutations whereas thermodynamic properties such as the difference in Gibbs free energy are virtually unaffected. Here, we comment on (bio-) physical concepts how non-covalent bonds are characterized and we highlight the limitations of these concepts. Furthermore, we consistently link molecular binding properties of DSG2 with the macroscopic stability of cellular networks overexpressing a distinct DSG2 species. Finally, on the basis of DSG2 binding kinetics, we draft a biophysically inspired hypothesis of a molecular pathomechanism leading to ARVC.

Obstructive Sleep Apnoea: A Risk Factor for Hypertension

Ozaifa Kareem¹, Masood Tanvir², Amreen Naqash¹, and G. N. Bader^1*

¹Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal Srinagar, Kashmir, India

²Department of General Medicine, Government Medical College Srinagar, India

Obstructive Sleep Apnoea (OSA) is the most prevalent condition among sleep disordered breathing that leads to increased risk of cardiovascular (CV) and cerebrovascular morbidity and mortality. The most common comorbidity associated with OSA is systemic hypertension (HTN). Various epidemiological studies suggest a link between OSA and hypertension that involves complex interactions between various pathophysiological mechanisms and metabolic risk factors. OSA causes changes in normal physiological functions during nocturnal apneic episodes which in-turn lead to daytime hypertension. The widely accepted mechanisms by which the OSA contributes to the development of hypertension include sympathetic activation, inflammation, oxidative stress, and endothelial dysfunction. OSA and hypertension coexist in millions of people and both have been associated with heart disease, stroke, and premature death. Worldwide the prevalence of hypertension in OSA is estimated between 30 and 70%, thus setting it off as a major public health problem. Furthermore, not only has OSA been implicated in causing new hypertension but also it is said to promote resistant hypertension in already existent hypertensive patients, which may further grim the clinical and therapeutic outcomes. It is necessary to recognize the underlying OSA in-order to decrease the overall healthcare burden in terms of rigorous anti-hypertensive therapy instituted to OSA subjects. The review summarizes an up-to-date scenario of obstructive sleep apnoea as a cause of systemic hypertension and the overall cardiovascular risks.

Novel Rat Models for Atherosclerosis

Huaqing Chen^1*, Dali Li¹, Mingyao Liu^1,2*

¹Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, China

²Institute of Biosciences and Technology, Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, Houston, Texas, USA

Mouse models have been widely used in atherosclerosis research and related therapy development. However, data suggested that it was difficult to translate discovery in mice to human. Thanks to the fast development and optimization in gene editing technology, atherosclerotic models in rats generated recently provide more options for different studies and could make a difference to the situation which is exclusively dependent on mouse. Here we reviewed novel rat models for atherosclerosis generated through genetic approaches in recent years, including Ldl receptor (Ldlr) and apolipoprotein e (Apoe) knockout rats. The phenotypes in hyperlipidemia, atherosclerosis, as well as related inflammatory responses, were compared. These models developed typical atherosclerosis. More importantly, some of them present certain advantages over mouse models. These not only provide novel options for animal models of atherosclerosis, but also will benefit future investigations of atherosclerotic pathology and anti-atherosclerotic therapeutics.