Top Banner
Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine [email protected] www.imbm.sk
71

Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Jul 03, 2020

Download

Documents

dariahiddleston
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Page 1: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Endothelial dysfunctionChronic venous disease

Roman Gardlík, MD, PhD

Institute of Pathophysiology

Institute of Molecular Biomedicine

[email protected]

www.imbm.sk

Page 2: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Endothelium

• A type of epithelium that lines the interior surfaceof blood vessels and lymphatic vessels

• Single layer of squamous endothelial cells withtight junctions

Page 3: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine
Page 4: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine
Page 5: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Figure 1. Endothelium and permeability.

William C. Aird Circ Res. 2007;100:158-173

Copyright © American Heart Association, Inc. All rights reserved.

Page 6: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Endothelial cell

• Large amounts of vesicles

and caveolae along the luminal

surface - transendothelial

transport of biologically active

substances

Page 7: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Endothelium

• Mesodermal origin

• EC are aligned and elongated in direction of flow

• EC line the entire circulatory system – one of thelargest organ systems

• Unique functions

Page 8: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Endothelium

• Fluid filtration (glomeruli)

• Barrier function

• Blood vessel tone (vasodilation and vasoconstriction)

• Hemostasis

• Hormone trafficking

• Inflammation - neutrophil recruitment

• Angiogenesis

• Secretion of mediators – normal vascular function

Page 9: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Barrier function

Page 10: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Figure 2. Endothelium and leukocyte trafficking.

William C. Aird Circ Res. 2007;100:158-173

Copyright © American Heart Association, Inc. All rights reserved.

Page 11: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine
Page 12: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Figure 4. Mechanisms of EC heterogeneity.

William C. Aird Circ Res. 2007;100:158-173

Copyright © American Heart Association, Inc. All rights reserved.

Page 13: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Endothelial dysfunction

• Systemic pathological state of the endothelium

• Imbalance between vasodilating and vasoconstricting substances produced by theendothelium

• Shift of the balance in favour of vasoconstrictive, pro-inflammatory and pro-thrombotic effects

• Mainly due to reduced bioavailability and bioactivity of nitric oxide (NO)

Page 14: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Vasodilation

• Nitric oxide

• EDHF

• Prostacyclin

• Acetylcholine

• Bradykinin

Page 15: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Nitric oxide

• Most abundant free radical in the body

• Halflife of NO is affected by its chemical reactionand inactivation by superoxide anion

• .O2- + .NO → ONOO-

Page 16: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Shear stress

• A stress state where the stress force is paralell to thesurface of the vessel (as opposed to normal stress, where the stress is vertical) – frictional force

• Force exerted on vessel wall / cross-sectional area

• NO is released after corrupted shear stress in the vessel– vasodilation

• NO mediated vasodilation restores shear stress

• If chronic – upregulation of inflammatory cytokines –endothelial dysfunction

Page 17: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Protective effects of NO

• Smooth muscle relaxation and vasodilation

• Lowering blood pressure

• Reducing proliferation of vascular smooth muscle

• Inhibition of platelet aggregation

• Inhibition of expression of VCAM and ICAM

Page 18: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine
Page 19: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Vasoconstriction

• Endothelin-1

• Prostaglandin H2

• Thromboxane A2

• ROS

• Endothelium-bound ACE – angiotensin II

Page 20: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Regulatory Functions of the EndotheliumNormal Dysfunction

Vasodilation Vasoconstriction

NO, PGI2, EDHF,

BK, C-NP

ROS, ET-1, TxA2,

A-II, PGH2

Thrombolysis Thrombosis

Platelet Disaggregation

NO, PGI2

Adhesion Molecules

CAMs, P,E Selectins

Antiproliferation

NO, PGI2, TGF-, Hep

Growth Factors

ET-1, A-II, PDGF, ILGF, ILs

Lipolysis Inflammation

ROS, NF-B

PAI-1, TF-α, Tx-A2tPA, Protein C, TF-I, vWF

LPLVogel R

Page 21: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine
Page 22: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine
Page 23: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Consequences of ED

• ED as progenitor of atherosclerosis (ED is presentlong before onset of symptoms)

• ED as predictor of future cardiovascular events

Page 24: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Oxidative stress

• Imbalance between production of reactive oxygenspecies and ability of the system to detoxify thereactive intermediates or to repair the damage

• Key mechanism of endothelial dysfunction

• OS + ED are major factors for atherosclerosis

Page 25: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine
Page 26: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine
Page 27: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine
Page 28: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

ED in disease

• Cardiovascular disease

• Diabetes

• Transplant vasculopathy

• Autoimmune diseases

• Celiac disease and irritable bowel syndrome

• Hematologic disorders

• Neurocognitive disorders

• Cirrhosis

Page 29: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

1. ED in diabetes

• T1DM, T2DM

• Pathogenesis unclear

• Multifactorial etiology of ED

• 1. Insulin resistance

• 2. Pro-inflammatory signalling

• 3. Oxidative stress

• 4. Protein kinase C

• 5. Hyperglycemia

Page 30: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Insulin resistance in ED

• Insulin activates vasoprotective pathways• PI3K/Akt – eNOS expression and activation

• In contrast, MAPK/ERK pathway promotes ET-1 and cellular proliferation

• In physiological conditions – PI3K predominates

• Insulin resistance – PI3K deficiency, MAPK predominates – proatherogenic signalling

Page 31: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Roberts and Porter 2013

Page 32: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Pro-inflammatory signalling in ED

• Adipose tissue produces inflammatory cytokines

• TNFalpha, free fatty acids, RAGE activate NFkBthat further stimulates expression of inflammatorygenes in endothelium

• Reduction of NO expression

Page 33: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Oxidative stress in ED

• OS as a unifying mechanism of endothelial injury

• OS leads to diminished NO bioavailability• Direct degradation of NO

• Alterations in functional capacity of eNOS

Page 34: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

2. ED in hypertension

• ED as an early event in pathophysiology of essential hypertension that contributes to subclinical target organ damage and progression of atherosclerosis

• Defective endothelial L-arginine/NO pathway

• Impaired responsiveness to exogenous NO

• Reduced generation of platelet NO

• In the presence of oxidatove stress

• Pro-inflammatory, pro-atherosclerotic, pro-thrombotic phenotype

Page 35: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Mechanism of ED in hypertension

• Hypertension as cause rather than consequence of endothelial dysfunction

• Hypertension-induced oxidative stress

Page 36: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Measuring endothelial function

• 1950s – endothelium as a dynamic organ with diversecapabilities

• Invasive methods

• 1992 – Celermajer et al. proposed first non-invasivemethod for assessment of endothelial function -diameter of superficial femoral and brachial arteries

• At rest

• During reactive hyperemia (endothelium-dependentdilatation)

• After sublingual nitroglycerin (endothelium-independentdilatation)

Page 37: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Vascular markers of ED

• Quantitative coronary angiography

• MRI

• PET

• Invasive measurement of forearm blood flow (FBF) by venous occlusion plethysmography

Page 38: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Vascular markers of ED

• Non-invasive measurement• Flow-mediated dilation (FMD) – macrovascular function

• Peripheral arterial tonometry – microvascular function

• Laser Doppler flowmetry

Page 39: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

ED in periodontitis

Page 40: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine
Page 41: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine
Page 42: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine
Page 43: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

ED treatment

• Treatment should target the underlyingcomorbidity that lead to ED

• Life style modification – diet, exercise, smoking cessation, weight reduction

• NO pathways – L-arginine, PDE-I

• Receptor and enzyme pathways – beta blockers, ACE-I, angiotensin receptor blockers, statins, aspirin

Page 44: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Secondary endothelial therapy

• Preserve the function of the already injuredendothelium to delay progression of cardiovasculardisease

• Statins, ACE-I, beta blockers, endothelin antagonists

Page 45: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Control questions

• What are the 3 main vasodilators?

• Define shear stress

• How oxidative stress leads to ED?

• Which functions of endothelium are dysbalanced / predominate in ED?

• What is the standard method for measurement of endothelial dysfunction?

Page 46: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

• Endothelial barrier dysfunction in septic shockhttps://www.youtube.com/watch?v=yl6R_3Jrs_s

• NO and vasodilationhttps://www.youtube.com/watch?v=echVKswxTqQ

• Vascular endotheliumhttp://www.authorstream.com/Presentation/nitinpuram-1516566-vascular-endothelium/

https://www.youtube.com/watch?v=yl6R_3Jrs_s
https://www.youtube.com/watch?v=echVKswxTqQ
http://www.authorstream.com/Presentation/nitinpuram-1516566-vascular-endothelium/
Page 47: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

A short break

Page 48: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Venous insufficiencyVarices

Page 49: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Venous system of lower limbs

• Superficial

• Perforator

• Deep

Page 50: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Chronic venous disease

• Condition in which the veins cannot pump enoughblood back to the heart

• 20% of Western population

• Varicose veins

• Chronic venous insufficiency

Page 51: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Chronic venous disease

• Causes:

• Deep vein thrombosis

• Arteriovenous fistula

• Phlebitis

• Thrombophilia

• Obesity

Page 52: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Varicose veins

• Dilated, often palpable, subcutaneous veins withreversed blood flow

• Mostly in legs

• 30% of population (18% men, 42% women)

• Risk factors: unknown, age, sex, pregnancy, obesity, family history

Page 53: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Pathogenesis

• Reflux

• Obstruction

• Varicose veins: • Increased amount of collagen• Decreased number of smooth muscle cells and elastin

• Disorganization of muscle components, disruption of elastin fibres and fibrosis

• Weakness of vein wall leads to dilatation and enlargement of the valve ring – the vein is unable to work properly - reflux

Page 54: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Pathogenesis

• Descending theory – the process starts proximallyand expands distal

• Ascending theory – tributaries become dilated and incompetent and only thereafter the main trunksand junctions

Page 55: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Pathogenesis

• Obstruction

• Acute obstruction occurs in deep vein thrombosis

• Chronic obstruction caused by post-thromboticchanges – stenosis, occlusion, rigidity of vein wall

• Obstruction + reflux – in 55% of symptomaticpatients

Page 56: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine
Page 57: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Evaluation

• Clinical features: swelling, stasis, skin changes, ulceration

• Symptoms: limb pain, itching, restless legs, nocturnal leg cramps, heaviness, discomfort

• Pain

Page 58: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Pain

• Assessed by visual-analogue scale, type and frequency of analgesic use

• Absent in 20% patients

• The only feature in 10% patients

• Is relieved by leg elevation, support stockings, walking

Page 59: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

CEAP classification

• Clinical

• Etiologic

• Anatomical

• Pathophysiological

• CVI = C3-C6

Page 60: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine
Page 61: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

CEAP

Page 62: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Adjunctive scoring system

Page 63: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Imaging

• Duplex ultrasound scan

Page 64: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Complications

• Deep vein thrombosis

• Skin changes

• Thrombophlebitis – thrombus in superficial vein

• Leg ulcers (3% patients)

• Bleeding

Page 65: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Treatment

Page 66: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Treatment

• Goals: • Alleviate symptoms• Prevent severe complications (ulcers)

• 1. Endothermal ablation of the saphenous vein –burn the vein from inside (radiofrequecy or laser)

• 2. Foam sclerotherapy

• 3. Surgery

• 4. Compression hosiery (only if no otherintervention is suitable)

Page 67: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Advice

• Weight loss

• Light to moderate physical activity

• Avoid factors that make symptoms worse

• When and where to seek further medical help

Page 68: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Treatment in pregnancy

• Pregnancy can exacerbate symptoms of varicoseveins and cause new ones

• No intervention in pregnancy (increases risk of thrombosis)

• Compression hosiery should be used

Page 69: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine
Page 70: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

Control questions

• Two mechanisms of CVI

• What does CEAP mean?

• What is the link between CVI and ED?

• Diagnostic methods

• How to know the most up-to-date methods of therapy?

Page 71: Endothelial dysfunction Chronic venous disease · Endothelial dysfunction Chronic venous disease Roman Gardlík, MD, PhD Institute of Pathophysiology Institute of Molecular Biomedicine

• [email protected]


Related Documents
Endothelial Dysfunction in HIV - InTech - Open Science Open Minds

Endothelial Dysfunction in HIV - InTech - Open Science Open....

Category: Documents
12(S)-HETE mediates diabetes induced endothelial dysfunction by … · 2020-06-24 · 1 12(S)-HETE mediates diabetes induced endothelial dysfunction by activating intracellular endothelial

12(S)-HETE mediates diabetes induced endothelial dysfunction...

Category: Documents
Research Article Vitamin B6 Prevents Endothelial Dysfunction ...downloads.hindawi.com/journals/jdr/2016/1748065.pdfResearch Article Vitamin B6 Prevents Endothelial Dysfunction, Insulin

Research Article Vitamin B6 Prevents Endothelial Dysfunction...

Category: Documents
Endothelial Dysfunction

Endothelial Dysfunction

Category: Documents
High selenium induces endothelial dysfunction via ...epubs.surrey.ac.uk/845246/1/PhD thesis Matshediso Zachariah 2017.… · High selenium induces endothelial dysfunction via endoplasmic

High selenium induces endothelial dysfunction via...

Category: Documents
Research Article Endothelial Dysfunction of Patients with ...downloads.hindawi.com/journals/ijvm/2016/3805380.pdf · Research Article Endothelial Dysfunction of Patients with Peripheral

Research Article Endothelial Dysfunction of Patients with...

Category: Documents
Endothelial Dysfunction in Tristetraprolin-deficient Mice Is Not ...

Endothelial Dysfunction in Tristetraprolin-deficient Mice Is...

Category: Documents
ENDOTHELIAL TRPV4 DYSFUNCTION IN A STREPTOZOTOCIN …

ENDOTHELIAL TRPV4 DYSFUNCTION IN A STREPTOZOTOCIN …

Category: Documents
Endothelial dysfunction in cerebral aneurysms

Endothelial dysfunction in cerebral aneurysms

Category: Documents
Neurovascular dysfunction, inflammation and endothelial activation ...

Neurovascular dysfunction, inflammation and endothelial...

Category: Documents
Fredrick Owala: Oxidative Stress and Endothelial Dysfunction in Diabetic Vasculature

Fredrick Owala: Oxidative Stress and Endothelial Dysfunction...

Category: Documents
Endothelial dysfunction Venous insufficiency and varices · Endothelial dysfunction Venous insufficiency and varices Roman Gardlík, MD, ... MAPK/ERK pathway promotes ET -1 and

Endothelial dysfunction Venous insufficiency and varices ·...

Category: Documents