Endothelial cells

endothelial cells

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

7. 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).

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

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

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

11. 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

12. Endothelium in cardiovascular disease

13. 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

14. Endothelium in sepsis

15. Endothelium in angiogenesis Physiological Endometrium P lacenta W ound healing H air growth Pathological Tumour angiogenesis

16. 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)

17. 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 B lockade of a single GF (e.g. VEGF) may inhibit tumor induced vascular growth Eg : Bevacizumab

18. 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.

19. 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 .)

20. 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)