Cardiovascular disease -- Atherosclerosis and the immune system
2021-07-06
(Press-News.org) Medical researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich have uncovered how signal proteins of the immune system regulate the development of atherosclerosis.
Atherosclerosis is one of the most common causes of death in Germany. The condition is characterized by the build-up of cholesterol and other fatty metabolites in the arterial wall directly below the endothelial cell layer, which is in direct contact with the bloodstream. This process results in constriction of the artery, which obstructs blood flow and can trigger heart attacks and strokes. Atherosclerosis is generally treated with drugs that reduce the concentration of lipids in the circulation, often using compounds called statins. However, statins effectively reduce the risk of cardiovascular disease in only 35 to 40% of the patients treated. The remaining 60% fail to respond to the medication. This has prompted the search for other drug targets. Since atherosclerosis is linked to chronic inflammatory processes, the immune system might offer new therapeutic options for tackling the disease. A group of researchers led by Professor Esther Lutgens and Dr. Dorothee Atzler at the LMU Medical Center have now elucidated an important component of the immune reaction involved in atherogenesis.
Immunotherapy as a treatment for atherosclerosis
Lutgens and her team at the Institute for Cardiovascular Prevention (Director: Prof. Dr. Christian Weber) and at the University of Amsterdam have now shown that the interaction between proteins called CD40L and CD40 represents a promising drug target for the suppression of atherosclerosis. The protein CD40L is synthesized by, and expressed on the surface of specialized cells of the immune system. It is recognized by the CD40 protein, a membrane-bound receptor that is expressed on antigen-presenting cells. However, CD40L also binds to receptors on other cell types that have diverse physiological functions. Using a mouse model, the LMU researchers deleted the gene for CD40L specifically in T cells and platelets as well as its counterpart, CD40, on dendritic cells. They then crossed these mice with a strain that is particularly prone to develop atherosclerosis.
Secretion of interferon-gamma by T-cells is known to stimulate immune functions, but the CD40L-deficient T-cells were found to secrete less interferon-gamma than those in which the gene is intact. In addition, further experiments indeed showed that, in the absence of CD40L in T-cells, the atherosclerotic plaques that formed were smaller and more stable. This suggests that inhibition of CD40L could enhance the stability of atherosclerotic plaques, and thus reduce the incidence of heart attacks induced by the rupture of blood vessels.
Similar results were obtained in a mouse strain that was unable to produce CD40 in dendritic cells. Deletion of CD40L in platelets, on the other hand, had no effect on the incidence of atherosclerosis, but it was associated with a reduction in atherosclerosis-associated clot formation.
"Our results provide clear evidence for differential, cell-type-specific functions of the CD40L/CD40 interaction in the context of atherosclerosis, and this has implications for therapeutic strategies that focus on this signaling pathway," says Lutgens. Her group is now extending their studies of the effects of CD40 und CD40L to other cell types, with the aim of developing drugs that can inhibit the functions of these proteins in a cell-specific fashion. In principle, this could be done by using either small-molecule inhibitors or bifunctional antibodies with different binding sites.
INFORMATION:
ELSE PRESS RELEASES FROM THIS DATE:
2021-07-06
Dysmenorrhea, that is, frequent severe and painful cramps during menstruation from abnormal contractions of the uterus, is the most common of all gynecological disorders. It affects between 16-91% of girls and women of reproductive age, of whom 2%-29% have symptoms severe enough to restrict their daily activity. Now, for the first time, researchers from China Medical University Hospital in Taiwan have shown that long-term exposure to air pollutants such as nitrogen and carbon oxides and fine particulate matter greatly raises the risk of developing dysmenorrhea. Based on long-term data on air quality and public health from national databases, they show that the risk to develop dysmenorrhea ...
2021-07-06
A study led by University of Barcelona researchers and carried out together with more than 1,650 students and their family members from 18 educational centres in Barcelona shows that citizen science is a valid approach able for doing high quality science, and in this case, able to provide nitrogen dioxide values with an unprecedented resolution and to assess the impact of the pollution in the health of their inhabitants.
The journal Science of the Total Environment has published the results of a study carried out by the research group OpenSystems of the University of Barcelona, the Barcelona Institute for Global Health (ISGlobal), promoted by La Caixa Foundation ...
2021-07-06
Participants at the 6th Joint Science Conference of the Western Balkans Process have developed a "10 Point Plan" to control the coronavirus pandemic in the Western Balkans. Participants at the virtual two-day meeting also discussed priorities for the time after the pandemic in the Western Balkans and South East Europe. These include a decent healthcare system, climate neutrality, reduction of air and water pollution, and the digitalization of education, public administration, industry and healthcare. The conference was jointly organized by the German National Academy of Sciences Leopoldina and the Polish Academy of Sciences as part of the Western Balkans ...
2021-07-06
Although hypomorph mammals (or equids) are currently represented by only one genus ('Equus') and just a handful of species of horses, donkeys and zebras, they were more diverse during the Eocene epoch (between 56 and 33.9 million years ago). One of the most widespread groups in Europe, which was an archipelago at that time, were the palaeotheriidae, named after the genus 'Palaeotherium', described in 1804 from fossils originating in the quarries of Montmartre (Paris) by the famous French naturalist George Cuvier.
The international Journal of Vertebrate Paleontology has recently published a paper on a study led by Leire Perales-Gogenola describing two new species of palaeotheriidae mammals that inhabited the subtropical landscape of Zambrana (Álava) ...
2021-07-06
Big hydropower plants are an important source of clean and cheap electricity for many countries in Southeast Asia. However, dams harm the environment and have dire consequences on local communities. Building more dams would therefore pose major trade-offs between electricity supply and environmental protection.
A team of scientists based in Singapore showed that these two challenges can be decoupled. Their study, titled "Solar energy and regional coordination as a feasible alternative to large hydropower in Southeast Asia", recently published in Nature Communications, showed that there are more sustainable pathways to a clean energy future (refer to figure below).
Building on high resolution mathematical models of the Thai, Laotian, and Cambodian ...
2021-07-06
Researchers from Skoltech and the Mental Health Research Center have found 22 lipids in the blood plasma of people with schizophrenia that were associated with lower symptom improvement over time during treatment. These can help track resistance to medication that affects over a third of patients. The paper was published in the journal Biomolecules.
Studies suggest that up to 34% of people living with schizophrenia can be resistant to two or more antipsychotic medications used to treat the disorder. Individual responses vary greatly, and there are no satisfactory biomarkers of treatment response yet, which can often turn finding the right medication into a painful ...
2021-07-06
TAMPA, Fla. (July 6, 2021) - All it takes is three consecutive nights of sleep loss to cause your mental and physical well-being to greatly deteriorate. A new study published in Annals of Behavioral Medicine looked at the consequences of sleeping fewer than six hours for eight consecutive nights - the minimum duration of sleep that experts say is necessary to support optimal health in average adults.
Lead author Soomi Lee, assistant professor in the School of Aging Studies at the University of South Florida, found the biggest jump in symptoms appeared after just one night of sleep loss. The number of mental and physical problems steadily got worse, peaking on day three. At that point, research shows the human body got relatively used to repeated sleep loss. But that all ...
2021-07-06
Announcing a new article publication for BIO Integration journal. In this article the authors Daowei Lin, Zhixiao Han, Yanni Fu, Xiaoqiu Zhu, Jin Li, Hui Xu, Jing Wen, Fei Wang and Mingyan Guo from Sun Yat-sen University, Guangdong, China, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China and University of Virginia, Charlottesville, VA, USA discuss how interscalene brachial plexus block combined with general anesthesia attenuates stress and inflammatory response in arthroscopic shoulder surgery.
In arthroscopic shoulder surgery, general ...
2021-07-06
Singapore, 7 July 2021 - In 1966, The Beatles cemented the plight of lonely older people in the popular imagination with the iconic 'Eleanor Rigby', a song that turned pop music on its head when it stayed at number one on the British charts for four weeks. Today, the impact of loneliness in old age on life and health expectancy has been categorically quantified for the first time in a study by scientists at Duke-NUS Medical School (Singapore), Nihon University (Tokyo, Japan) and their collaborators, published in the Journal of the American Geriatrics Society.
"We found that lonely older adults can expect to live a shorter life than their peers who don't perceive themselves as ...
2021-07-06
Announcing a new article publication for BIO Integration journal. In this article the authors Xiao'en Shi, Xu Zhang, Xinlu Zhang, Haizhen Guo and Sheng Wang from Tianjin University, Tianjin, China discuss the integration of reactive oxygen species generation and prodrug activation for cancer therapy.
The combination of chemotherapeutic drugs and reactive oxygen species (ROS) can improve cancer treatment outcome. Many ROS-generation strategies can specifically consume tumor-inherent oxygen and generate ROS, resulting in amplified ROS level and aggravated hypoxia. Therefore, the ROS generation strategy can integrate with prodrug activation strategy to realize synergetic therapy.
In recent years, stimuli-responsive nanomedicines have ...
LAST 30 PRESS RELEASES:
[Press-News.org] Cardiovascular disease -- Atherosclerosis and the immune system
