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Summary Cardiovascular Disease; Lecture 1 tm 12.
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Cardiovascular Disease Summary1-Introduction Lecture
History of the cardiovascular system
Aristotle (384-322 BC)
Recognized different taxa in biology, based on their circulation
• 2 major life forms:
» Simple life form: Cold-blooded
» Complex life form: Warm-blooded
• 3 complexities of life forms:
» vegetative soul: necessary for nutrition, growth and reproduction (present in all
life forms)
» sensitive soul: sensory system necessary for sensation and mobility (animals en humans)
» Rational soul: has the ability of thought and reflection (humans only)
Erasistratus (305-250 BC)
First functional description of a vascular system
Transport of essential substances (air, blood and movement) through the body via specific vessels;
arteries, veins and neurons.
• Veins: Transport of nutrients in the form of blood
• Arteries: Life in the form of air from the lungs
• Nerves: Movement in the form of an unidentified substance (electricity)
Galen (131-215)
All vessels contain blood:
Arteries: Blood originating from the heart that distributes oxygen
Veins: Blood originating from the liver that distributes nutrients
Theory of 4 body fluids (humores) and temperaments:
» Phlegm (slime): relaxed, peaceful, quiet, and easy-going.)
» Blood: talkative, enthusiastic, active, and social.)
» Gele gal: independent, decisive, goal-oriented, and ambitious.)
» Zwarte gal: introvert, analytical and detail-oriented
Disbalances between these humores would lead to sickness and can
be cured by bloodletting
William Harvey (1578-1657); First anatomical description of a closed cardiovascular system including
the pulmonary system.
>Discovery that arteries carry blood away from the heart and veins carry blood back to the heart.
>Discovery of the heart as pump for two separated circulatory pathways (systemic and pulmonary)
Antonie van Leeuwenhoek (1632-1723); Inventor of the microscope Use of microscopes for cell
biology studies
Marcello Malpighi (1628-1694); used the microscope > Arteries and veins are connected via a
capillary network
,Aristotle 400 BC
Erasistratus
Galen
Harvey
Malpighi 1661 AD
After 2000 yrs of research a complete picture of the
cardiovascular system was there…
Wilhelm His Sr. (1831-1904) Discovery of the endothelium and
its origin during embryology
Wilhelm His Jr. (1863-1934);
Bundle of His Origin of the heart beat starts in specific cells of
the heart.
Henryk Hoyer (1891-1965); Discovery of the lymphatic system
Florence Sabin (1871-1953) Discovery that blood, blood vessels
and circulating blood cells originate from the same precursor;
the (heme)angioblast
ric Jaffe (1948) Isolation and culture of endothelial cells (1971)
Michael Gimbrone (1943) Discovery of VEGF (Vascular
Permeability Factor)
Judah Folkman (1933-2008) Mechanisms of Tumor-angiogenesis
The culture of endothelial cells has sparked the molecular research into the regulation of vascular
function
Endothelial cell function
The cardiovascular system:
1. Heart
» Muscle of 200-250gr.
» 3.5x109 contractions/life time
(ca. 100.000 contractions/day)
2. Blood vessels
» 100.000 km / 350m2 (approx. size of a tennis veld)
3. Lymph vessels
,Cardiovascular Disease;
All cardiovascular diseases contain some form of endothelial dysfunction!
Development of the cardiovascular system: angiogenesis > results in vascular system
Why is the capillary network different between organs?
The capillary network is differently organized because in all the organs > different function. In the
liver; leaky for uptake of waste products. In the kidney; highly organized; kidney needs to filter all the
, blood. In the long alveoli; a lot of small capillaries close to the air sacs in order to make diffusion
efficiently. In the heart; highly dense network to feed the heart muscle cells.
Plasticity of the Endothelium
• Cellular plasticity
» Heterogeneity of the vasculature
» Organ-specific EC phenotypes
» Endothelial-Mesenchymal Transition
• Functional plasticity
» Barrier function (Adhesion molecules)
» Immunology (Leukocyte migration)
» Thrombogenicity
» Vasomotor function (NO, ET1)
» Vascularisation (vasculogenesis & angiogenesis)
Endothelium plasticity is very important in maintaining vascular health:
Endothelial Barrier Function
• Tight Junctions (Occludins)
» Sealing of the EC layer (membrane fusion)
• Adherence Junctions (VE-Cadherin)
» Cell-cell connections (distribution of force)
» Gap Junctions
» EC-EC Communication (connection of
cytoplasm)
• Importance of the EC Barrier
» Formation of gradients
» Pressure (high in vasculature, low in tissue)
» Metabolites (active transport from blood into
tissues)
» Inhibition of leukocyte migration
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