A5086508722- Erythrocyte Function and Pathophysiology
- Nitric Oxide and Endothelin Effects
- Adipokines, Inflammation, and Metabolic Diseases
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- COVID-19 Clinical Research Studies
- Neuroscience of respiration and sleep
- Extracellular vesicles in disease
- Blood properties and coagulation
- Adenosine and Purinergic Signaling
- Long-Term Effects of COVID-19
- Receptor Mechanisms and Signaling
- Regulation of Appetite and Obesity
- Heart Rate Variability and Autonomic Control
- MicroRNA in disease regulation
- Cardiac Imaging and Diagnostics
- Cardiac Ischemia and Reperfusion
- Circular RNAs in diseases
- Thermoregulation and physiological responses
- Hemoglobin structure and function
- Protein Tyrosine Phosphatases
- Lipid metabolism and disorders
- Metabolomics and Mass Spectrometry Studies
- Neonatal Health and Biochemistry
- Cancer-related molecular mechanisms research
- Heme Oxygenase-1 and Carbon Monoxide
Karolinska University Hospital
2019-2025
Karolinska Institutet
2019-2025
We recently showed that red blood cells (RBCs) from patients with type 2 diabetes mellitus (T2DM-RBCs) induce endothelial dysfunction through a mechanism involving arginase I and reactive oxygen species. Peroxynitrite is known to activate in cells. Whether peroxynitrite regulates activity RBCs, whether it involved the cross-talk between RBCs vasculature T2DM, unclear elusive. The present study was designed test hypothesis induced by T2DM-RBCs driven upregulation of arginase. were isolated...
Current knowledge regarding mechanisms underlying cardiovascular complications in patients with COVID-19 is limited and urgently needed. We shed light on a previously unrecognized mechanism unravel key role of red blood cells, driving vascular dysfunction infection. establish the presence profound persistent endothelial vivo COVID-19. Mechanistically, we show that targeting reactive oxygen species or arginase 1 improves mediated by cells. These translational observations hold promise...
Red blood cells (RBCs) induce endothelial dysfunction in type 2 diabetes (T2D), but the mechanism by which RBCs communicate with vessel is unknown. This study tested hypothesis that extracellular vesicles (EVs) secreted act as mediators of T2D. Despite a lower production EVs derived from T2D patients (T2D RBC-EVs), their uptake was greater than healthy individuals (H RBC-EVs). RBC-EVs impaired endothelium-dependent relaxation and this effect attenuated following inhibition arginase EVs....
Abstract Background and Purpose MicroRNA (miR)‐210 function in endothelial cells its role diabetes‐associated dysfunction are not fully understood. We aimed to characterize the miR‐210 study therapeutic potential diabetes. Experimental Approach Two different diabetic mouse models ( db/db Western diet‐induced), knockout transgenic mice, isolated vessels human were used. Key Results levels lower aortas from than control mice. Endothelium‐dependent relaxation (EDR) was impaired this restored by...
Abstract Background Patients with familial hypercholesterolemia (FH) display high levels of low‐density lipoprotein cholesterol (LDL‐c), endothelial dysfunction, and increased risk premature atherosclerosis. We have previously shown that red blood cells (RBCs) from patients type 2 diabetes induce dysfunction through arginase 1 reactive oxygen species (ROS). Objective To test the hypothesis RBCs FH (FH‐RBCs) elevated LDL‐c dysfunction. Methods results FH‐RBCs >5.0 mM induced following 18‐h...
Abstract Background Conflicting evidence exists concerning the cardioprotective efficacy of remote ischemic conditioning as an adjunct to primary percutaneous intervention (PCI) in ST‐elevation myocardial infarction (STEMI) and data on long‐term outcomes are scarce. We evaluated final infarct size by cardiac magnetic resonance (CMR) performed 6 months after anterior STEMI treated with clinical up 3 years event. Methods One hundred fifteen patients were randomized per‐postconditioning...
Red blood cells (RBCs) mediate cardioprotection via nitric oxide-like bioactivity, but the signaling and identity of any mediator released by RBCs remains unknown. We investigated whether exposed to hypoxia release a cardioprotective explored nature this mediator. Perfusion isolated hearts subjected ischemia-reperfusion with extracellular supernatant from mouse resulted in improved postischemic cardiac function reduced infarct size. Hypoxia increased export cyclic guanosine monophosphate...
Red blood cells (RBCs) are suggested to play a role in cardiovascular regulation by exporting nitric oxide (NO) bioactivity and ATP under hypoxia. It remains unknown whether such beneficial effects of RBCs protective patients with acute myocardial infarction. We investigated from ST-elevation infarction (STEMI) protect against ischemia-reperfusion injury effect involves NO purinergic signaling the RBCs. STEMI undergoing primary coronary intervention healthy controls were administered...
Reduced nitric oxide (NO) bioactivity in red blood cells (RBCs) is critical for augmented myocardial ischemia-reperfusion injury type 2 diabetes. This study identified the nature of "NO bioactivity" by stimulating intracellular NO receptor soluble guanylyl cyclase (sGC) RBCs. sGC stimulation RBCs from patients with diabetes increased export cyclic guanosine monophosphate and activated cardiac protein kinase G, thereby attenuating injury. These results provide novel insight into RBC signaling...
The mechanisms underlying endothelial dysfunction in type 1 and 2 diabetes (T1DM T2DM) are unresolved. red blood cells (RBCs) with increased arginase activity induce T2DM, but the implications of RBCs role inhibition T1DM unexplored. We aimed to investigate differences function patients focus on arginase. Thirteen 26 matched for HbA1c sex were included. In vivo endothelium-dependent -independent vasodilation (EDV EIDV), assessed by venous occlusion plethysmography before after administration...
Red blood cells from patients with STEMI and systemic inflammation induce endothelial dysfunction ex vivo. The RBC-induced is mediated through increased arginase 1 a shift in the redox balance toward oxidative stress. Inhibition of or free radicals attenuates impairment function. study suggests that red deserve attention as key player STEMI.
Abstract Background Recently, we have demonstrated that red blood cells (RBCs) from individuals with type 2 diabetes (T2D-RBCs) induce endothelial dysfunction. However, the mechanism by which RBCs communicate vessel is unknown. Extracellular vesicles (EVs) are actively secreted practically all cell types, including RBCs, and represent a novel of intercellular communication. involvement EVs RBC in development dysfunction remains to be elucidated. Purpose This study was designed test...
It is well established that altered purinergic signaling contributes to vascular dysfunction in type 2 diabetes (T2D). Red blood cells (RBCs) serve as an important pool for circulating ATP and the release of from RBCs response physiological stimuli impaired T2D. We recently demonstrated patients with T2D (T2D RBC) key mediators endothelial dysfunction. However, it remains unknown whether involved induced by dysfunctional Here, we evaluated acetylcholine-induced endothelium-dependent...
The mechanisms underlying rupture of a coronary atherosclerotic plaque and development myocardial ischemia-reperfusion injury in ST-elevation infarction (STEMI) remain unresolved. Increased arginase 1 activity leads to reduced nitric oxide (NO) production increased formation reactive oxygen species due uncoupling the NO-producing enzyme endothelial NO synthase (eNOS). This contributes dysfunction, instability susceptibility acute infarction.The purpose this study was test hypothesis that...
<p dir="ltr">Background</p><p dir="ltr">Complications of atherosclerotic cardiovascular disease remain the leading cause death globally. Patients with diabetes and patients coronary artery are at severely increased risk developing complications disease. An early presentation is a dysfunctional state vascular endothelium, known as endothelial dysfunction, which prominent in type 2 mellitus (T2DM) The underlying mechanisms dysfunction largely dependent on reduced...
<p dir="ltr">Background</p><p dir="ltr">Complications of atherosclerotic cardiovascular disease remain the leading cause death globally. Patients with diabetes and patients coronary artery are at severely increased risk developing complications disease. An early presentation is a dysfunctional state vascular endothelium, known as endothelial dysfunction, which prominent in type 2 mellitus (T2DM) The underlying mechanisms dysfunction largely dependent on reduced...
Abstract Background Red blood cells (RBCs) are known to export cardioprotective nitric oxide (NO) bioactivity. Although, RBCs contain a functional soluble guanylyl cyclase (sGC), the signalling behind of NO bioactivity remains unclear. Impairment in has been suggested contribute augmented cardiac ischemia-reperfusion injury type 2 diabetes (T2D). We hypothesized that increased signaling by stimulation sGC protects from myocardial release signal. Purpose To investigate whether sGC,...
Abstract Background Vascular injury has been implicated as a major cause of clinical complications in patients with coronavirus disease 2019 (COVID-19). Autopsy studies have revealed destruction the endothelial cell lining, which might explain cardiovascular alterations arising from infection. However, data demonstrating dysfunction during ongoing infection are sparse, and underlying mechanisms still largely unknown. Red blood cells (RBCs) affected by COVID-19 their structure function,...
Background: Vascular injury has been implicated as a major cause of clinical complications in patients with coronavirus disease 2019 (COVID-19) based on autopsy studies showing destruction the endothelial architecture. Red blood cells (RBCs) are affected by COVID-19 alterations their structure and function, possibly altering progress. Objectives: This study was designed to test hypothesis persistent dysfunction that RBCs act mediators COVID-19. Methods results: displayed profound vivo...
Abstract Background Red blood cells (RBCs) are known to regulate cardiovascular function under hypoxic conditions and mediate cardioprotection via nitric oxide (NO)-like bioactivity. However, the molecular signalling behind this effect identity of any mediator released by RBCs remain unknown. Previous studies revealed that NO activates soluble guanylate cyclase (sGC) increases formation second messenger cyclic guanosine monophosphate (cGMP) in RBCs. The functional role during...
Abstract Background The mechanisms underlying rupture of a coronary atherosclerotic plaque and development myocardial ischemia-reperfusion injury in ST-elevation infarction (STEMI) remain unknown. Increased arginase-1 activity leads to reduced nitric oxide production increased formation reactive oxygen species due uncoupling the endothelial synthase (eNOS). These events lead dysfunction, instability susceptibility acute infarction. Experimental studies have shown that expression are...
Abstract Background The important role of inflammation in atherosclerotic plaque progression and instability leading to myocardial infarction has been widely demonstrated. C-reactive protein (CRP) shown be predictive value cardiovascular disease. red blood cell (RBC) is an regulator function through nitric oxide bioactivity oxidative stress ischemic heart Also, arginase-1 greatly influence RBCs cause endothelial dysfunction. However, the mechanisms by which regulate vascular patients with...
Abstract Background Arginase is involved in the development of ischemia-reperfusion injury by regulating nitric oxide (NO) bioactivity via competition with NO synthase (NOS) for their common substrate L-arginine. Erythrocytes are known to contain high levels arginase that may reduce export cardioprotective bioactivity. Aim To determine role 1 erythrocytes cardiac protection against myocardial injury. Methods A tie2 cre-flox mouse model, which was deleted (Arg 1-KO) hematopoietic and...
Abstract Background Red blood cells (RBC) are suggested to act as important mediators in the regulation of cardiovascular function by exporting nitric oxide (NO) bioactivity and ATP under hypoxic/ischemic conditions. In addition, RBCs known protect from ischemia-reperfusion injury via export NO experimental settings. However, it remains unknown if such beneficial effects protective patients with acute myocardial infarction. Purpose To investigate whether ST-elevation infarction (STEMI)...