Trevor P. Fidler
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View article: Spatial Transcriptomics Reveals <i>CXCL12</i> ⁺ Fibroblasts as Central Immune Organizers through CXCR4 Signaling in Abdominal Aortic Aneurysm
Spatial Transcriptomics Reveals <i>CXCL12</i> ⁺ Fibroblasts as Central Immune Organizers through CXCR4 Signaling in Abdominal Aortic Aneurysm Open
BACKGROUND Abdominal aortic aneurysm (AAA) is characterized by sterile inflammation, immune cell infiltration, and stromal remodeling that progressively weaken the aortic wall, leading to life-threatening aortic rupture. The molecular mech…
View article: Macrophage EHD1 promotes inflammation and stabilizes sortilin to accelerate atherosclerosis
Macrophage EHD1 promotes inflammation and stabilizes sortilin to accelerate atherosclerosis Open
Background Macrophages are key players in the pathogenesis of atherosclerosis. They trigger immune responses through their cell-surface receptors. However, how macrophages regulate those receptors in response to pro-inflammatory stimuli is…
View article: Aggressive Cholesterol Lowering Normalizes Atherosclerosis Regression in <i> Jak2 <sup>V617F</sup> </i> Mice
Aggressive Cholesterol Lowering Normalizes Atherosclerosis Regression in <i> Jak2 <sup>V617F</sup> </i> Mice Open
Background The Jak2 V617F ( Jak2 VF ) mutation is an important cause of both clonal hematopoiesis of indeterminate potential (CHIP) and myeloproliferative neoplasms (MPN). Mouse models of Jak2 VF CHIP and MPN show accelerated atheroscleros…
View article: IL-18 inhibition enlarges lesions, necrotic cores and thickens fibrous caps in <i>Jak2<sup>V617F</sup></i> clonal hematopoiesis-driven atherosclerosis
IL-18 inhibition enlarges lesions, necrotic cores and thickens fibrous caps in <i>Jak2<sup>V617F</sup></i> clonal hematopoiesis-driven atherosclerosis Open
Background Inflammasome activation promotes atherosclerosis in clonal hematopoiesis (CH). Active inflammasomes secrete both IL-1β and IL-18. Plasma IL-18 levels are elevated in Jak2 VF CH. Genetic deficiency of IL-18 has been shown to redu…
View article: Macrophages redeploy functional cancer cell surface proteins following phagocytosis
Macrophages redeploy functional cancer cell surface proteins following phagocytosis Open
Macrophage-mediated phagocytosis is a vital innate immune process altered in cancer. We show here that tumor-associated macrophages (TAMs) redeploy intact cell surface proteins from cancer cells to their own cell surface. We initially obse…
View article: Genetic modification of inflammation- and clonal hematopoiesis–associated cardiovascular risk
Genetic modification of inflammation- and clonal hematopoiesis–associated cardiovascular risk Open
Clonal hematopoiesis of indeterminate potential (CHIP) is associated with an increased risk of cardiovascular diseases (CVDs), putatively via inflammasome activation. We pursued an inflammatory gene modifier scan for CHIP-associated CVD ri…
View article: Hematopoietic NLRP3 and AIM2 Inflammasomes Promote Diabetes-Accelerated Atherosclerosis, but Increased Necrosis Is Independent of Pyroptosis
Hematopoietic NLRP3 and AIM2 Inflammasomes Promote Diabetes-Accelerated Atherosclerosis, but Increased Necrosis Is Independent of Pyroptosis Open
Serum apolipoprotein C3 (APOC3) predicts incident cardiovascular events in people with type 1 diabetes, and silencing of APOC3 prevents both lesion initiation and advanced lesion necrotic core expansion in a mouse model of type 1 diabetes.…
View article: Hematopoietic NLRP3 and AIM2 inflammasomes promote diabetes-accelerated atherosclerosis, but increased necrosis is independent of pyroptosis
Hematopoietic NLRP3 and AIM2 inflammasomes promote diabetes-accelerated atherosclerosis, but increased necrosis is independent of pyroptosis Open
Serum apolipoprotein C3 (APOC3) predicts incident cardiovascular events in people with type 1 diabetes and silencing of APOC3 prevents both lesion initiation and advanced lesion necrotic core expansion in a mouse model of type 1 diabetes…
View article: Hematopoietic NLRP3 and AIM2 inflammasomes promote diabetes-accelerated atherosclerosis, but increased necrosis is independent of pyroptosis
Hematopoietic NLRP3 and AIM2 inflammasomes promote diabetes-accelerated atherosclerosis, but increased necrosis is independent of pyroptosis Open
Serum apolipoprotein C3 (APOC3) predicts incident cardiovascular events in people with type 1 diabetes and silencing of APOC3 prevents both lesion initiation and advanced lesion necrotic core expansion in a mouse model of type 1 diabetes…
View article: Genetic modification of inflammation and clonal hematopoiesis-associated cardiovascular risk
Genetic modification of inflammation and clonal hematopoiesis-associated cardiovascular risk Open
Clonal hematopoiesis of indeterminate potential (CHIP) is associated with an increased risk of cardiovascular diseases (CVD), putatively via inflammasome activation. We pursued an inflammatory gene modifier scan for CHIP-associated CVD ris…
View article: Endogenous SOD2 (Superoxide Dismutase) Regulates Platelet-Dependent Thrombin Generation and Thrombosis During Aging
Endogenous SOD2 (Superoxide Dismutase) Regulates Platelet-Dependent Thrombin Generation and Thrombosis During Aging Open
Background: Reactive oxygen species (ROS) contribute to platelet hyperactivation during aging. Several oxidative pathways and antioxidant enzymes have been implicated; however, their mechanistic contributions during aging remain elusive. W…
View article: Erythroid lineage Jak2V617F expression promotes atherosclerosis through erythrophagocytosis and macrophage ferroptosis
Erythroid lineage Jak2V617F expression promotes atherosclerosis through erythrophagocytosis and macrophage ferroptosis Open
Elevated hematocrit is associated with cardiovascular risk; however, the causality and mechanisms are unclear. The JAK2V617F (Jak2VF) mutation increases cardiovascular risk in myeloproliferative disorders and in clonal hematopoiesis. Jak2V…
View article: Inhibition of JAK2 Suppresses Myelopoiesis and Atherosclerosis in Apoe−/− Mice
Inhibition of JAK2 Suppresses Myelopoiesis and Atherosclerosis in Apoe−/− Mice Open
Objective Increased myelopoiesis has been linked to risk of atherosclerotic cardiovascular disease (ACD). Excessive myelopoiesis can be driven by dyslipidemia and cholesterol accumulation in hematopoietic stem and progenitor cells (HSPC) a…
View article: Loss of MCU prevents mitochondrial fusion in G <sub>1</sub> -S phase and blocks cell cycle progression and proliferation
Loss of MCU prevents mitochondrial fusion in G <sub>1</sub> -S phase and blocks cell cycle progression and proliferation Open
The mitochondrial Ca 2+ uniporter enables ATP production to match energy demands during the cell cycle.
View article: Glucose Metabolism Is Required for Platelet Hyperactivation in a Murine Model of Type 1 Diabetes
Glucose Metabolism Is Required for Platelet Hyperactivation in a Murine Model of Type 1 Diabetes Open
Patients with type 1 diabetes mellitus (T1DM) have increased thrombosis and platelet activation. The mechanisms for platelet hyperactivation in diabetes are incompletely understood. T1DM is accompanied by hyperglycemia, dyslipidemia, and i…
View article: Macrophage Inflammation, Erythrophagocytosis, and Accelerated Atherosclerosis in <i>Jak2</i> <sup> <i>V617F</i> </sup> Mice
Macrophage Inflammation, Erythrophagocytosis, and Accelerated Atherosclerosis in <i>Jak2</i> <sup> <i>V617F</i> </sup> Mice Open
Rationale: The mechanisms driving atherothrombotic risk in individuals with JAK2 V617F ( Jak2 VF ) positive clonal hematopoiesis or myeloproliferative neoplasms are poorly understood. Objective: The goal of this study was to assess atheros…
View article: Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function
Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function Open
(Cell Reports 20, 881–894; July 25, 2017) In the originally published version of this article, the author name Andrew S. Weyrich was erroneously written as Andrew S. Weyrch. The name has now been corrected online. The authors regret this e…
View article: Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function
Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function Open
(Cell Reports 20, 881–894; July 25, 2017) In the originally published version of this article, the Supplemental Experimental Procedures were accidentally omitted. The Supplemental Experimental Procedures now appear with the article online.…
View article: Glucose Transporter 3 Potentiates Degranulation and Is Required for Platelet Activation
Glucose Transporter 3 Potentiates Degranulation and Is Required for Platelet Activation Open
Objective— On activation, platelets increase glucose uptake, glycolysis, and glucose oxidation and consume stored glycogen. This correlation between glucose metabolism and platelet function is not well understood and even less is known abo…
View article: Superoxide Dismutase 2 is dispensable for platelet function
Superoxide Dismutase 2 is dispensable for platelet function Open
Summary Increased intracellular reactive oxygen species (ROS) promote platelet activation. The sources of platelet-derived ROS are diverse and whether or not mitochondrial derived ROS, modulates platelet function is incompletely understood…