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Karolinska universitetssjukhuset
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John Pernow Group

Endothelial dysfunction in atherosclerotic cardiovascular disease

About

Our research aims to explore novel mechanisms behind the progression of atherosclerosis and to develop new therapeutic strategies reduce the risk of myocardial infarction. We focus on mechanism causing endothelial dysfunction, especially by the risk factors diabetes and high cholesterol. We are also conducting research on how to limit the injury to the myocardium occurring during a myocardial infarction.

Endothelial and cardiac injury induced by dysfunctional RBC in type 2 diabetes. From the publikation Pernow et al. Cardiovasc Res 2019;115:1596-1605.

Research

Atherosclerotic cardiovascular disease including coronary artery disease (CAD) and myocardial infarction remains leading cause of morbidity and mortality. Despite recent progress, the mechanisms remain unclear. Occurrence of endothelial dysfunction primarily characterized by reduced availability of nitric oxide (NO) increased oxidative stress is an early factor during development of CAD and tissue injury during ischemia-reperfusion.

Our research is focused on the identification of disease mechanisms behind endothelial dysfunction, and development of novel therapeutic strategies to improve endothelial function in coronary artery disease (CAD) and limit the extent of myocardial infarction.

This is of particular importance in diabetes and hyperlipidemia which considerably increases the risk for CAD. We have identified key regulators of NO including the enzyme arginase that is upregulated in CAD and diabetes and reciprocally regulates NO formation and oxidative stress. Targeting arginase improves endothelial function and protects against myocardial ischemia-reperfusion injury both by increasing NO production and reducing the formation of reactive oxygen species (ROS).

Our recent data suggest an intriguing interaction between red blood cells (RBCs) and the endothelium in the development of cardiovascular injury in type 2 diabetes. This effect appears to be driven by increased arginase activity and ROS formation in RBCs in type 2 diabetes.

Ongoing projects

In ongoing projects we investigate:

  • the effect of RBCs from different patient groups with risk factors for and developed atherosclerotic cardiovascular disease on cardiac and endothelial dysfunction
  • the signaling mechanisms underlying cardiac and vascular injury caused by RBC from patients with and animal models of type 2 diabetes, hypercholesterolemia and myocardial infarction
  • the effect of pharmacological interventions on RBC and endothelial function in these patient groups
  • the impact of co-morbidities on cardioprotective effects of pharmacological and ischemic conditioning on acute myocardial infarction

Research methods and models

We perform translational studies ranging from molecular to clinical studies. Molecular studies are focused on understanding of the role of NO signaling pathway in RBCs, endothelial cells and the vascular wall. Additional approaches are focused on signaling by non-coding RNA. Experimental models include isolated heart preparations, isolated vessels, cell culture and in vivo models of myocardial infarction. We also perform investigations of endothelial function in humans, which include early interventional studies exploring novel targets in patients with CAD and risk factors. Finally, the group performs randomized clinical studies with functional and clinical endpoints.

Significance

The project will provide novel insights into molecular mechanisms driving development of CAD and myocardial ischemia-reperfusion injury. Targets identified in experimental studies are tested in early clinical interventional studies that will provide the basis for novel therapeutic strategies.

Group leader

John Pernow, professor, senior physician, john.pernow@ki.se

Group members

Zhichao Zhou, principal researcher, docent, zhichao.zhou@ki.se

Aida Collado Sánchez, assistant professor, aida.collado.sanchez@ki.se

David Ersgård, biomedical scientist, david.ergard@ki.se

Ames Hakam, administrator, ames.hakam@ki.se

Jiangning Yang, senior research specialist, jiangning@ki.se

Helena Karlsson, research nurse, helena.karlsson.2@ki.se

Magnus Mossfeldt, IT specialist, magnus.mossfeldt@ki.se

Tong Jiao, postdoctoral researcher, tong.jiao@ki.se

Karin Ljung, postdoctoral researcher, karin.ljung@ki.se

Kesavan Manickam, postdoctoral researcher, kesavan.manickam@ki.se

Álvaro Santana Garrido, postdoctoral researcher, alvaro.santana.garrido@ki.se

Ayman Bakeer, PhD student, ayman.bakeer@ki.se

Kari Feldt, PhD student, kari.feldt@ki.se

Elena Fortin, PhD student, elena.fortin@ki.se

Rawan Humoud, PhD student, rawan.humoud@ki.se

Eftychia Kontidou, PhD student, eftychia.kontidou@ki.se

Andreas Liliequist, PhD student, andreas.liliequist@ki.se

Ulrika Löfström, PhD student, ulrika.lofstrom@ki.se

Safi Moayad Al-Azzawy, PhD student, safi.moayad.alazzawy@ki.se

Jenny Petersson, PhD student, jenny.petersson@ki.se

Elina Rautio, PhD student, elina.rautio@ki.se

Ulrika Reistam, PhD student, ulrika.reistam@ki.se

Ayse-Gül Öztürk, PhD student, ayse-gul.ozturk@ki.se

Artur Fedorowski, adjunct professor, artur.fedorowski@ki.se

Anna Norhammar, adjunct professor, anna.norhammar@ki.se

Cecilia Linde, senior professor, cecilia.linde@ki.se

Mai-Lis Hellenius, professor emerita, mai-lis.hellenius@ki.se

Lars Rydén, professor emeritus, lars.ryden@ki.se

Karin Schenck-Gustafsson, professor emerita, karin.schenck-gustafsson@ki.se

Eva Sundman, adjunct lecturer, docent, eva.sundman@ki.se

Ava Azari, affiliated to research, ava.azari@ki.se

Mikael Dellborg, affiliated to research, mikael.dellborg@ki.se

Fredrik Gadler, affiliated to research, docent, fredrik.gadler@ki.se

Viveca Gyberg, affiliated to research, viveca.gyberg@ki.se

Isabelle Johansson, affiliated to research, isabelle.johansson@ki.se

Juliane Jurga, affiliated to research, juliane.jurga@ki.se

Oskar Kövamees, affiliated to research, oskar.kovamees@ki.se

Matthias Lidin, affiliated to research, matthias.lidin@ki.se

Ali Mahdi, affiliated to research, ali.mahdi@ki.se

Linda Mellbin, affiliated to research, linda.mellbin@ki.se

Viveca Ritsinger, affiliated to research, viveca.ritsinger@ki.se

Andreas Rück, affiliated to research, andreas.ruck@ki.se

Nondita Sarkar, affiliated to research, nondita.sarkar@ki.se

Magnus Settergren, affiliated to research, docent, magnus.settergren@ki.se

Moa Simonsson, affiliated to research, moa.simonsson@ki.se

Marcus Ståhlberg, affiliated to research, docent, marcus.stahlberg@ki.se

Helena Sundling, affiliated to research, helena.sundling@ki.se

Peder Sörensson, affiliated to research, docent, peder.sorensson@ki.se

John Tengbom, affiliated to research, john.tengbom@ki.se

Eva Wallgren, affiliated to research, eva.wallgren@ki.se

Marita Wallin, affiliated to research, marita.wallin@ki.se

Selected publications

About CMM

The Center for Molecular Medicine (CMM) is a foundation instituted by the Stockholm County Council (Region Stockholm). CMM is at the heart of a close partnership with the Karolinska University Hospital and Karolinska Institutet, fueling advancements in biomedical and clinical research.

Contact

Center for Molecular Medicine Foundation, org. nr. 815201-3689

Karolinska University Hospital L8:05

Visionsgatan 18

171 76 Stockholm, Sweden

communication@cmm.se

CMM
Karolinska institutet
Karolinska universitetssjukhuset