in vitro models of human blood vessel wall dysfunction v1

  • Research type

    Research Study

  • Full title

    Use of human umbilical cord-derived vascular cells and human adult blood cells to study mechanisms of vascular dysfunction and repair

  • IRAS ID

    212225

  • Contact name

    Ann Ellis

  • Contact email

    ann.ellis@bartshealth.nhs.uk

  • Sponsor organisation

    Barts Health

  • Duration of Study in the UK

    5 years, 0 months, 0 days

  • Research summary

    The endothelium is a thin layer of cells that lines all blood vessels and is continuously challenged by a complex mixture of circulating blood cells, nutrients and blood constituents. Healthy endothelium limits the adherence of immune cells to the vessel wall and ensures that inflammatory responses are resolved appropriately. However, when the endothelial cell monolayer becomes inflamed or damaged a condition known as ‘endothelial dysfunction’ develops. This increases naturally with age but is accelerated by conditions such as obesity and diabetes, known risk factors for cardiovascular disease. In arteries the condition encourages blood cells to adhere to endothelial cells and migrate into the vessel wall. Migrated cells become activated and produce pro-inflammatory damaging factors that cause vascular smooth muscle cells to proliferate, accumulate calcium (‘calcification’) and encourage development of fatty plaques (atherosclerosis) which can result in a heart attack. When endothelial dysfunction occurs in microvessels the ability of the tissue to repair is diminished because healthy endothelial cells are required for a process called ‘angiogenesis’, which is essential for healing. A specific type of circulating blood cell (‘endothelial progenitor cell’) helps repair areas of dysfunctional endothelium by interacting with endothelial cells to encourage angiogenesis.
    We will use human umbilical cords, discarded after birth, to isolate endothelial cells (HUVEC) and smooth muscle cells (HUASMC). We will also use red blood cells, and different white blood cell (leukocyte) populations isolated from normal human blood. Our studies seek to understand more about the genes and proteins involved in regulating interaction of blood cells with the endothelium during inflammation, vascular smooth muscle cell calcification, and how endothelial progenitor cells control angiogenesis and tissue repair. The long term aim of this research is to identify new therapeutic targets to support novel strategies that limit age- and disease-associated vascular dysfunction and encourage normal tissue repair.

  • REC name

    East of England - Cambridge South Research Ethics Committee

  • REC reference

    16/EE/0395

  • Date of REC Opinion

    2 Nov 2016

  • REC opinion

    Further Information Favourable Opinion