[John Vane, 1927-2004, the pharmacologist of the vascular endothelium [corrected]]

F Chast1

  • 1Service de Pharmacologie-Toxicologie de l'Hôtel-Dieu, 1, Place du Parvis Notre-Dame, F 75181 Paris Cedex 04, France. francois.chast@htd.ap-hop-paris.fr

Insights

John Vane

Area of Science:

  • Biochemistry and Pharmacology: Focuses on enzyme mechanisms and drug discovery.
  • Cardiovascular Medicine: Investigates aspirin's role in preventing stroke and heart attacks.

Background:

  • John Vane's research elucidated aspirin's mechanism in low-dose cardiovascular prevention.
  • His work highlighted the vascular endothelium's physiological importance and as a drug target.

Discussion:

  • Vane developed the 'blood-bathed organ cascade' assay for sensitive mediator monitoring.
  • Discovery of prostacyclin, a potent inhibitor of platelet aggregation.
  • Explained anti-inflammatory drug action via cyclooxygenase inhibition, impacting prostaglandin and thromboxane production.

Key Insights:

  • Established aspirin's critical role in cardiology through prostaglandin pathway modulation.
  • Identified prostacyclin as a key mediator in vascular homeostasis and platelet function.
  • The discovery of COX-2 led to targeted anti-inflammatory drugs (coxibs).

Outlook:

  • Vane's foundational work continues to influence cardiovascular drug development.
  • Understanding COX-1 and COX-2 pathways remains crucial for managing inflammation and cardiovascular disease.
  • Further research into endothelial function and prostaglandin signaling holds therapeutic potential.

Related Concept Videos

Overview of the Vascular System01:20

Overview of the Vascular System

The vascular system comprises an extensive network of arteries, capillaries, and veins. The vascular system can be broadly divided into the blood and lymphatic systems. Typically, blood vessels can be categorized into three histological regions: tunica intima, tunica media, and tunica adventitia. The tunica intima consists of a single layer of endothelial cells attached to the basal lamina. Underlying the basal lamina is a connective tissue layer and an elastic lamina that gives stability and...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
The Blood-brain Barrier00:49

The Blood-brain Barrier

Overview
Anatomy of the Circulatory System02:03

Anatomy of the Circulatory System

The human circulatory system consists of blood, blood vessels that carry blood away from the heart, around the body, and back to the heart, and the heart itself, which acts as a central pump. The systemic circuit supplies blood to the whole body, the coronary circuit supplies blood to the heart, and the pulmonary circuit supplies blood flow between the heart and lungs.
Blood Flow01:29

Blood Flow

Blood is pumped by the heart into the aorta, the largest artery in the body, and then into increasingly smaller arteries, arterioles, and capillaries. The velocity of blood flow decreases with increased cross-sectional blood vessel area. As blood returns to the heart through venules and veins, its velocity increases. The movement of blood is encouraged by smooth muscle in the vessel walls, the movement of skeletal muscle surrounding the vessels, and one-way valves that prevent backflow.