The document discusses the functions of endothelial cells, which form the inner lining of blood vessels. Some key points: - Endothelial cells regulate vascular tone, coagulation, inflammation, permeability and more. - Dysfunctions in endothelial cells are associated with diseases like diabetes, hypertension and atherosclerosis. - Endothelial cells produce nitric oxide and prostacyclin which cause vasodilation and inhibit platelet activation. - Damage and dysfunction of endothelial cells plays a role in the development of many cardiovascular and other diseases. - Various drugs and lifestyle factors like antioxidants and omega-3 fatty acids can help improve endothelial function.

1. Functions of Endothelium in Heart and
Disease
Dr. Chandan Kumar

2. • Endothelial cells - Mesodermal in origin
• Forms as interface between circulating blood or
lymph in the lumen and the rest of the vessel wall
• Composed of a single layer of cells that lines the
interior surface of all blood vessels.
• Estimated to representing a weight of 1.5 kg and
covering 4000-7000 sq. Meter (equivalent to six
football fields)

3. • They are flattened cells,having a thickness of
about 0.5 µm,and are 100µm long , 10 µm wide.
• Their lozenge shapes are juxtaposed in a mosaic
such that their long axis is oriented in the
direction of blood flow.
• Nuclei are also elongated in the direction of
blood flow.
• Attached to a basal membrane rich in collagen
and glycoproteins , forming a complex interface
between the circulation and the platelet
activating , procoagulant vascular matrix.

5. • ECs contain Weibel-Palade bodies, intracellular membrane-bound
storage organelles for von Willebrand factor.
• Antibodies to VWF and/or platelet-endothelial cell adhesion molecule
1 (PECAM-1 or CD31, a protein localized to interendothelial
junctions) can be used to identify ECs immunohistochemically.
• Endothelium is multifunctional -synthetic and metabolic properties
• ECs maintain a non-thrombogenic blood-tissue interface, modulate
vascular resistance, metabolize hormones, regulate inflammation, and
affect the growth of other cell types, particularly SMCs.
• As a selectively permeable monolayer, controls the transfer of small
and large molecules into the vascular wall.

6. • Endothelial function in health and disease
Homeostatic Phenotype Dysfunctional Phenotype
Vasodilation Vasoconstriction
Antithrombotic Prothrombotic
Profibrinolytic Antifibrinolytic
Anti-inflammatory Proinflammatory
Antiproliferative Proproliferative
Antioxidant Prooxidant
Permselectivity Impaired barrier function

9. • Tight EC junctions can loosen under the influence of
hemodynamic factors (e.g., high blood pressure) and/or
vasoactive agents (e.g., histamine in inflammation).
• EC lining Hepatocyte cords or in Renal glomeruli are
fenestrated , while endothelium in the CNS create a very
impermeable blood-brain barrier

12. • Nitric oxide-vasodilatory properties, can limit platelet activation and
aggregation.
• Like NO, Prostacyclin produced by Ecs provides a vasodilatory
stimulus and also antagonizes platelet activation and aggregation.
• Thrombomodulin expressed on the surface of endothelial cells binds
thrombin at low concentrations and inhibits coagulation by
inactivating factors Va and VIIIa .
• Surface of ECs contains heparan sulfate glycosaminoglycans - an
endogenous antithrombotic coating to the vasculature

14. NITRIC OXIDE
• free radical gas.
• first identified as E D R F .
• At high concentration , fight against infectious organism and cancer
cell.
• At lower concentration helps in regulating the circulation and CNS.
• NO does not require receptor for its action ,when synthesized
immediately utilized.

16. • NO is produced in ECs by enzymatic conversion of L-
Arginine to citrulline via type 3 NO synthase (NOS).
• Endothelial NO diffuse into vascular smooth muscle- binds
gunanylate cyclase- increase cGMP production causing
relaxation through decrease in intracellular calcium
• Chronic upregulation of NO synthase occur in response to
episodic increase in coronary flow such as during exercise
training

18. E D H F :
• In blood vessels Endothelium-Derived
Hyperpolarizing Factor or EDHF is synthesized in
and released from the endothelium
• Action is to hyperpolarise vascular smooth muscle
cells, causing these cells to relax, allowing the blood
vessel to dilate.

19. • Disease having endothelial dysfunction:
• Diabetes
• Hypertension
• Stroke
• Angina
• Pulmonary hypertension
• Pre-Eclampsia
• Erectile dysfunction
• Raynaud’s disease
• Renal failure

21. • Increased intracellular glucose → formation of advanced
glycosylation end products (AGEs)→ bind to cell surface receptor.
• AGEs cross-link proteins (e.g collagen, extracellular matrix proteins),
accelerate atherosclerosis, promote glomerular dysfunction, reduce
nitric oxide synthesis, induce endothelial dysfunction, alter
extracellular matrix composition and structure.

24. • Asymmetric dimethylarginine (ADMA) is an endogenous
competitive inhibitor of nitric oxide (NO) synthase and it is
detectable in human urine and plasma synthesized from
endothelial cells.
• Increased ADMA concentration has a high prevalence in
hyperhomocysteinemia,CAD, hypercholesterolemia,DM,
hypertension,PAD, impaired renal function and other
diseases.
• ADMA is degraded by DDAH (Di methyl amino hydrolase)
into Citrulline and dimethylamine.

25. • Endothelium and Atherosclerosis
• Oxidation of LDL leads to atherosclerosis
• plasma and macrophage content of oxidized LDL in
coronary plaques correlate with severity of ACS.
• Impaired activity of NO leads to atherosclerosis,
vasoconstriction, platelet aggregation, smooth muscle cell
proliferation and migration, leukocyte adhesion and
oxidative stress
• Oxidized LDL cholesterol increases synthesis of caveolin-1,
which inhibits production of NO by inactivating eNOS

29. • Venous occlusion plethysmography has been used
to measure vasomotor responses of forearm
resistance vessels during infusion of acetylcholine
into the brachial artery.
• Vendy’s endothelial function measurement.

30. • Applied aspects
• ASPIRIN:
• Irreversible inhibition of cyclooxygenase
• Reduction of both Thromboxane A2 and prostacyclin
• PGI2 –produced by endothelial cells
• TXA2 –produced by platelet
• Endothelial cells produce new COX in a matter of hours
• For platelets COX level rises only after new platelet
formation (4-8) days
• Therefore, Aspirin reduces clot formation
• Prevent MI,unstable angina, TIA, Stroke

31. • Topical VEGF, PDGF, and FGF helps in wound healing.
• Statin therapy improve endothelium-dependent dilation
of coronary and peripheral arteries in patients with
hypercholesterolemia.Changes in FMD were not
correlated with decreases in total and LDL cholesterol.
Effects of statins on NO production via increased
availability of eNOS.
• Nebivolol cardioselective β-adrenoceptor antagonists
having beneficial effects on endothelial function via
augmentation of NO release , which is decreased in
plasma of cardiac syndrome X patients (Angina pectoris
with a normal coronary arteriogram.)

32. • Telmisartan possesses PPARγ agonistic properties
,and improves insulin resistance as well as vascular
endothelial dysfunction. PPARγ activation protect
endothelial function,by stimulation of endothelial
nitric oxide production.
• Ankylosing spondylitis, endothelial dysfunction is a
part of the disease and infliximab (anti TNF- α)
improves both endothelial dysfunction and
inflammatory disease activity, thus manage
spondylitis and its atherosclerotic complications

33. • Dietary modulation of endothelial function
• n−3 fatty acids or increased fish consumption can
reduce mortality in MI patients. Decrease
expression of adhesion molecules on the
endothelium and also decrease leukocyte-
endothelium interactions.
• Antioxidant vitamins have beneficial effects on
endothelial function by reducing cell adhesion
molecule expression and improving endothelium-
dependent vasodilation.
• folic acid in reducing the risk of CVD.Reduces
concentrations of plasma homocysteine

34. • L-Arginine is the substrate for nitric-oxide
synthase in the production of nitric oxide.
Improves endothelial function in patients with
CVD or hypercholesterolemia
• Mediterranean diet characterized by high
consumption of vegetables, fish, olive oil and
moderate wine consumption may have a positive
effect on endothelial function