The effect of pressure-induced mechanical stretch on vascular wall differential gene expression.
High blood pressure is responsible for the modulation of blood vessel morphology and function. Arterial hypertension is considered to play a significant role in atherosclerotic ischaemic heart disease, stroke and hypertensive nephropathy, whereas high venous pressure causes varicose vein formation and chronic venous insufficiency and contributes to vein bypass graft failure. Hypertension exerts differing injurious forces on the vessel wall, namely shear stress and circumferential stretch. Morphological and molecular changes in blood vessels ascribed to elevated pressure consist of endothelial damage, neointima formation, activation of inflammatory cascades, hypertrophy, migration and phenotypic changes in vascular smooth muscle cells, as well as extracellular matrix imbalances. Differential expression of genes encoding relevant factors including vascular endothelial growth factor, endothelin-1, interleukin-6, vascular cell adhesion molecule, intercellular adhesion molecule, matrix metalloproteinase-2 and -9 and plasminogen activator inhibitor-1 has been explored using ex vivo cellular or organ stretch models and in vivo experimental animal models. Identification of pertinent genes may unravel new therapeutic strategies to counter the effects of pressure-induced stretch on the vessel wall and hence minimise its notable complications.
Academic Section of Vascular Surgery, Department of Surgery and Cancer, Imperial College London, Charing Cross Hospital, London, UK.
M A
MA
Anwar
J
J
Shalhoub
C S
CS
Lim
M S
MS
Gohel
A H
AH
Davies
D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology; D001164:Arteriovenous Fistula / Q000503:physiopathology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000503:physiopathology*; D015870:Gene Expression; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008465:Mechanoreceptors / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000503:physiopathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013314:Stress, Mechanical; D014157:Transcription Factors / Q000502:physiology; D014652:Vascular Diseases / Q000503:physiopathology
D017382:Reactive Oxygen Species; D014157:Transcription Factors; D020782:Matrix Metalloproteinases