Endothelial cells line the blood vessels and form an interface between circulating blood elements and the vessel wall. They play a vital role in health by regulating vascular permeability, blood clotting, vasodilation, and angiogenesis. Endothelial dysfunction contributes to cardiovascular diseases like atherosclerosis and hypertension. Endothelial cells also support tumor growth by stimulating angiogenesis and are a target for cancer treatments that block blood vessel formation like bevacizumab.

1. ENDOTHELIAL CELLS IN
HEALTH AND DISEASE
PRESENTER: DR.JANANI MATHIALAGAN
MODERATOR: DR.ANANDRAJ VAITHY

2. OBJECTIVES
• ENDOTHELIAL CELLS
• FUNCTIONS OF NORMAL ENDOTHELIAL CELLS
• ROLE IN
• CARDIOVASCULAR DISEASE
• SEPSIS
• CANCER

3. WHAT ARE ENDOTHELIAL CELLS
• Mesodermal derived cells
• Forms the lining the blood vessels
• Forms an interface between circulating elements and the vessel which
contains it.

4. • Endothelial Precursor Cells (EPC) from marrow and pre-existing blood vessels
migrate to the site of injury or tumour growth.
• Differentiation of EPC forms a mature network of linking with existing vessels.

5. FUNCTIONS OF ENDOTHELIAL CELLS

6. ENDOTHELIAL HETEROGENICITY
EC’s exhibit different phenotype- both in structure & function
• Structural heterogeneity- obtained following electron microscopy
observations where differences in intercellular junctions
• continuous endothelium
• fenestrated endothelium
• discontinuous endothelium

8. PRODUCTS FROM ENDOTHELIAL CELLS
• von Willebrand factor (vWF)
• tissue factor
• platelet activating factor (hemostasis)
• Nitric oxide - vasodilator
Post injury, subendothelial collagen is exposed - attachment of platelets
(adhesion)
• prostacycline (inhibits platelet aggregation),
• protein S (a cofactor for protein C, which is an inhibitor of coagulation), and
• tissue plasminogen activator (activates fibrinolysis).

9. In brain
Formation of blood-
brain-barrier.

10. In lungs
Respiratory membrane
• selective phagocytic activity
• extract substances from blood
• Oxygen and cardon-di-oxide diffusion

11. Endothelial dysfunction
• Oxidative Stress
1) Decreased NO
2) Increased Endothelin ( ET-1 binds to Endothelin A and B receptors
in pulmonary vascular bed - potent vasoconstrictor)
• It is also a physiological process.

13. Endothelium in smoking
• Nicotine
• Opens up intercellular junction
• Allow large molecules to pass through the wall
• Toxins - degenerative changes in the blood vessels & lead to vascular
disease

14. Endothelium in cardiovascular disease

15. Endothelium in hypertension
• Angiotensin-converting-enzyme(ACE) is an endothelial enzyme
• Converts angiotensinogen I to angiotensinogen II.
• Angiotensin II is a potent vasoconstrictor.
• Important in pathogenesis of hypertension

16. Endothelium in sepsis

17. Endothelium in angiogenesis
• Physiological
Endometrium
Placenta
Wound healing
Hair growth
• Pathological
Tumour angiogenesis

18. Endothelium in malignancy
• EC growth supports metabolic requirement of tumor beyond few mm
(growth of primary & metastatic tumor)
• Possible pathogenesis involved
stimulation of EC
degradation of ECM
proliferation of EC & migration into tumor
Formation of new capillary tubes
• Tumor vessels are tortuous, dilated, uneven diameter, excessive
branching & shunting (lacks perivascular cells)

19. Endothelium in malignancy
Tumour cells - Acquired drug resistance of tumor (due to high intrinsic
mutation rate) --- major cause of treatment failure
But ECs are genetically stable
• EC provides nourishment to many tumor cells; tumor growth depends
on angiogenesis
Blockade of a single GF (e.g. VEGF) may inhibit tumor induced vascular
growth
Eg: Bevacizumab

20. Summary
• EC’s play a vital role in health and integrity of every tissue of the body
because apart from cartilage, every cell lies within a few µm of a
capillary.
• The diffusion limit of oxygen in tissue is only ≈ 100µm and can not
cross blood vessel thicker than that.
• Fine capillaries (10-15 µm) consist merely of endothelial cells and a
very fine basal lamina, thus helps in providing oxygen, nutrients &
metabolites.

21. Summary
• EC adjust their number & arrangement to accommodate local
requirement
• Involved in extending & remodeling the network of blood vessels to
enable tissue growth & repair.
• Dysfunction of EC has been implicated in virtually every type
vascular disease( Atherosclerosis, HTN etc.)

22. References
• Pathological basis of disease : Robbins & Cotran,8th edition
• Kawthalkar – Clinical pathology
• Harrison’s internal medicine: 17th edition
• Hematology : Basic Principles & Practise,5th edition( Hoffman)