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JOINT SESSION: Newly Described Functions in the Vascular Space

PhD Trainee
Sponsor: Scientific Committee on Megakaryocytes and Platelets||Scientific Committee on Thrombosis & Vascular Biology
Program: Scientific Program
Hematology Disease Topics & Pathways:
Fundamental Science, Bleeding and Clotting, Diseases, Biological Processes, Study Population
Saturday, December 7, 2024: 4:00 PM-5:35 PM
Room 25 (San Diego Convention Center)

Description:
Dysregulated interactions between platelets, immune cells, endothelial cells, and their plasma environment underlie numerous age-related diseases. This joint session will provide an integrated view of the vascular space and will highlight the cellular and molecular mechanisms underlying diseases that primarily afflict the elderly. Specifically, the session will focus on novel discoveries addressing how platelet and endothelial aging may affect neurodegenerative disorders and thrombotic disease, and immune thrombocytopenia (ITP), and will shed light into the role of fibrinolytic factors in shaping the pro-atherogenic plasma lipid profile.

Dr. Nerlov, will discuss how aging affects hematopoietic stem cells (HSCs). He will describe how increased HSC platelet bias due to how age-related increases in TGFbeta signaling is an evolutionarily conserved feature of murine and human hematopoiesis. The role of HSC platelet bias in suppressing lymphoid cell production during aging and how TGFbeta receptor inhibition can increase the ability of aged HSCs to support antiviral immunity will also be discussed.  

Dr. Cooper, will discuss the current understanding of ITP pathogenesis and how the results from novel treatments in ITP may depict different disease types in ITP. ITP is a common bleeding disorder with an increase in incidence after age 60. Understanding the disease phenotype and evolution is needed to improve patient outcomes. However, the diagnosis remains presumptive, and treatment is largely empiric, with many patients rotating through several treatments before having a platelet response.

Dr. Lesniewski will discuss the phenotype of the aging vasculature and the hematopathology underlying mechanisms and potential therapeutic strategies being explored to reverse arterial aging to reduce cardiovascular (CVD) risk in older adults. This is important since several factors contributing to dysfunction of the endothelium (i.e., oxidative stress and inflammation, deregulated nutrient sensing, and cellular senescence) increase with aging and could impact CVD risk.

Dr. Zheng will discuss research demonstrating that hepatocytes are an unappreciated source of tissue-type plasminogen activator (tPA), sense metabolic stresses, and impact the production of tPA and its inhibitor PAI1, thereby influencing the extent of fibrinolysis in obesity. She will introduce findings that tPA binds directly to hepatocyte apoB, preventing it from being loaded with lipids and assembled into lipoproteins. Conversely, tPA's inhibitor, PAI1, has the opposite effect, sequestering free tPA and preventing its interaction with apoB to promote VLDL assembly and increase apoB-lipoprotein cholesterol levels.

 

Co-chairs:
Lijun Xia, MD, PhD, Oklahoma Medical Research Foundation and Hartmut Weiler, PhD, Versiti Blood Research Institute
Disclosures:
Xia: Equilibra Bioscience: Consultancy.

Dysregulated interactions between platelets, immune cells, endothelial cells, and their plasma environment underlie numerous age-related diseases. This joint session will provide an integrated view of the vascular space and will highlight the cellular and molecular mechanisms underlying diseases that primarily afflict the elderly. Specifically, the session will focus on novel discoveries addressing how platelet and endothelial aging may affect neurodegenerative disorders and thrombotic disease, and immune thrombocytopenia (ITP), and will shed light into the role of fibrinolytic factors in shaping the pro-atherogenic plasma lipid profile.

Dr. Nerlov, will discuss how aging affects hematopoietic stem cells (HSCs). He will describe how increased HSC platelet bias due to how age-related increases in TGFbeta signaling is an evolutionarily conserved feature of murine and human hematopoiesis. The role of HSC platelet bias in suppressing lymphoid cell production during aging and how TGFbeta receptor inhibition can increase the ability of aged HSCs to support antiviral immunity will also be discussed.  

Dr. Cooper, will discuss the current understanding of ITP pathogenesis and how the results from novel treatments in ITP may depict different disease types in ITP. ITP is a common bleeding disorder with an increase in incidence after age 60. Understanding the disease phenotype and evolution is needed to improve patient outcomes. However, the diagnosis remains presumptive, and treatment is largely empiric, with many patients rotating through several treatments before having a platelet response.

Dr. Lesniewski will discuss the phenotype of the aging vasculature and the hematopathology underlying mechanisms and potential therapeutic strategies being explored to reverse arterial aging to reduce cardiovascular (CVD) risk in older adults. This is important since several factors contributing to dysfunction of the endothelium (i.e., oxidative stress and inflammation, deregulated nutrient sensing, and cellular senescence) increase with aging and could impact CVD risk.

Dr. Zheng will discuss research demonstrating that hepatocytes are an unappreciated source of tissue-type plasminogen activator (tPA), sense metabolic stresses, and impact the production of tPA and its inhibitor PAI1, thereby influencing the extent of fibrinolysis in obesity. She will introduce findings that tPA binds directly to hepatocyte apoB, preventing it from being loaded with lipids and assembled into lipoproteins. Conversely, tPA's inhibitor, PAI1, has the opposite effect, sequestering free tPA and preventing its interaction with apoB to promote VLDL assembly and increase apoB-lipoprotein cholesterol levels.

 

Claus Nerlov, PhD

University of Oxford, Oxford, United Kingdom

Nichola Cooper, MD

Imperial College, London, ENG, United Kingdom

Lisa Lesniewski, PhD

University of Utah Health, Salt Lake City, UT

Ze Zheng, MBBS, PhD

Medical College of Wisconsin; Versiti Blood Research Institute, Milwaukee, WI

See more of: Scientific Program