Invited review: activity-induced angiogenesis

Cardiovascular Physiology

Abstract

The dynamic biochemical and mechanical environment around blood vessels during muscle activity generates powerful stimuli for vascular remodelling. Ultimately, this must lead to a coordinated expansion of various elements of the cardiovascular system in order to support enhanced aerobic exercise. Vascular endothelial growth factor plays a central role, and understanding how this is regulated in vivo by changes in transcription and stability of mRNA, production of protein and interaction with other growth factors, is a continuing challenge. Exercise hyperaemia leads to an increase in microvascular shear stress, which stimulates endothelial release of nitric oxide, whilst proteolytic modification of the extracellular matrix is induced by mechanical deformation during cyclical contractions or muscle overload. These components of the exercise response lead to different forms of capillary growth, and subsequent expansion of the microcirculation may not have the same functional outcome. In vitro and in vivo studies have shown a complex interplay between different cytokines, receptors and mural cells in directing the necessary tissue re-organisation. The mechanisms involved in arteriogenesis are less well-understood than those of angiogenesis, but application of these data to understanding vascular remodelling in response to exercise may help resolve a range of cardiovascular dysfunction.

Keywords

Angiogenesis Exercise Growth factors Remodelling Skeletal muscle Training 

Abbreviations

Ang

angiopoietin

C:F

numerical capillary to fibre ratio

CD

capillary density

CHF

chronic (congestive) heart failure

EC

endothelial cells

ECM

extracellular matrix

eNOS

endothelial nitric oxide synthase

EPC

endothelial progenitor cells

FGF

fibroblast growth factor

HIF

hypoxia-inducible factor

MO2max

maximal oxygen consumption

MMP

matrix metalloproteinases

NOS

nitric oxide synthase

PDGF

platelet-derived growth factor

PGI2

prostacyclin

PlGF

placental growth factor

RTK

receptor tyrosine kinase

TGF

transforming growth factor

TIMPs

tissue inhibitors of matrix metalloproteinases

VEGF

vascular endothelial growth factor

VEGFR

VEGF receptor

VSM

vascular smooth muscle

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Angiogenesis Research Group, Centre for Cardiovascular SciencesUniversity of Birmingham Medical SchoolBirminghamUK

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