Molecular pathogenesis of subarachnoid haemorrhage
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Molecular pathogenesis of subarachnoid haemorrhage. Baiping Zhang, Kaare Gugleholm, Lorna B. Day, Shu Ye, Roy O. Weller, Ian N.M. Day 5 November 2002. Pathogenesis and the stages involved in the formation of saccular aneurysm Cellular and molecular architecture of the vessel wall

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Molecular pathogenesis of subarachnoid haemorrhage

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Molecular pathogenesis of subarachnoid haemorrhage

Molecular pathogenesis of subarachnoid haemorrhage

Baiping Zhang, Kaare Gugleholm, Lorna B. Day, Shu Ye, Roy O. Weller, Ian N.M. Day

5 November 2002


Molecular pathogenesis of subarachnoid haemorrhage

  • Pathogenesis and the stages involved in the formation of saccular aneurysm

  • Cellular and molecular architecture of the vessel wall

  • Molecular pathology

    • PKD1 gene and polycystin

    • COL3A1 and type III collagen

    • Fibrillin-1

    • Collagen IV and other basement membrane constituents

    • Alpha1-Antitrypsin (protease inhibitor)

  • Future focus


Subarachnoid haemorrhage sah

Subarachnoid haemorrhage (SAH)

  • Condition caused by the escape of blood from a cerebral artery into the subarachnoid space along the surface of the brain.

http://instruct.uwo.ca/anatomy/530/SagSin.gif


Molecular pathogenesis of subarachnoid haemorrhage

  • Mortality of diagnosed cases is about 40% within the first 30 days

  • Less then 25% have a good functional outcome and the disease has dramatic impact on the lives of carers and relatives.

Pritchard, Foulkes, Lang, & Neil-Dwyer. 2001


Schematic overview of contributory factors to subarachnoid haemorrhage

Schematic overview of contributory factors to subarachnoid haemorrhage

B. Zhang et al./ The International Journal of Biochemistry & Cell Biology 35 (2003) 1341-1360


Commonest sites for saccular aneurysms

Commonest sites for Saccular Aneurysms

B. Zhang et al./ The International Journal of Biochemistry & Cell Biology 35 (2003) 1341-1360


Molecular pathogenesis of subarachnoid haemorrhage

B. Zhang et al./ The International Journal of Biochemistry & Cell Biology 35 (2003) 1341-1360


Etiology involved in the formation of saccular aneurysms

Etiology involved in the formation of saccular aneurysms

  • Majority of aneurysms occur between the ages of 40 and 70

    • Ageing effects on the arteries

  • Increased incidence of saccular aneurysms in families with

    • Polycystic kidney disease

    • Fibromuscular dysplasia

    • Moyamoya disease

    • Marfan Syndrome

    • EDS type IV


Pkd1 gene and polycystin

PKD1 gene and polycystin

  • Adult polycystic kidney disease is an autosomal dominant disorder in which renal cysts form, leading to progressive loss of glomerular filtration and subsequently to renal failure and end-stage renal disease.

  • PKD1 gene causing (PKD)

    • Encodes for a protein named polycystin

  • Polycystin - participates in protein-protein and protein-carbohydrate interactions in the extracellular matrix

adpkd.cimr.cam.ac.uk/ buttons/pkd1_hs_350.gif


Col3a1 and type iii collagen

COL3A1 and type III collagen

  • Ehlers-Danlos Syndrome Vascular Type

    • Arterial rupture risk

    • Thin transparent skin

    • Early bruising

    • Joint laxity

    • Ligament weakness

    • Bowel rupture

  • (EDS type IV)

    • Defective collagen III synthesis

    • Vascular expression on COL3A1


Collagen iv and other basement membrane constituents

Collagen IV and other basement membrane constituents

  • Collagen IV defects cause Alport’s syndrome.

  • Alports syndrome characterized sensorineural hearing loss and haematuria.

    • Its is therefore plausible new hypothesis that defects in the basement membrane as well as defects in the elastic and medial layer may predispose intracranial aneurysms


Protease inhibitor alpha1 antitrypsin

Protease inhibitor (alpha1-Antitrypsin)

  • Most abundant and potent natural inhibitor of elastase.

  • Alpha1-Antitrypsin activity has been claimed to be reduced in both intracranial and abdominal aortic aneurysm.


Future focus

Future focus


Fibrillin 1 and fbn1

Fibrillin-1 and FBN1

  • Marfan syndrome is an autosomal dominant heritable disorder of connective tissue with prominent manifestations affecting the skeletal, ocular and cardiovascular systems.

  • Progressive dilation of the aortic root and aortic dissection and rupture are frequent, and mitral and aotic valve insufficiency may also occur early.

    • Caused by mutations in FBN1 gene encoding fibrilin-1

      • Mutations of this gene also cause type I fibrillinopathies


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