New insights into the role of matrix metalloproteinasesin heart angiogenesis induced by exercise

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Abstract

Angiogenesis induced by exercise has been observed in both cardiac and skeletal muscle andplays a fundamental role in maintaining tissue function adequate to the increase in metabolic requests.Mechanical and haemodynamic forces are strong starters of angiogenic process via regulation of secondarymediators such as vascular endothelial growth factor (VEGF). A crucial step of vessel sprouting is thedegradation of the basement membrane and remodelling of the extracellular matrix (ECM) by matrix metalloproteinases(MMPs). It has long been accepted that MMPs are involved in the angiogenesis, but the exactmechanisms are not well characterized. Cryptic fragments and neo-epitopes released by proteolysis of basementmembrane components by MMPs can promote or block capillary growth. MMPs are also involved inthe release and activation of growth factors embedded into ECM such as VEGF. In turn, it has been showed invitro that VEGF can stimulate endothelial and smooth muscle cells to produce MMPs suggesting a reciprocalrelationship between VEGF and MMPs. The expression patterns of MMPs are temporally dissociated by thoseof VEGF in vivo: MMPs and VEGF seem to be independently regulated and involved respectively in sproutformation and capillary proliferation. Little is known about the regulation of MMPs by exercise and the moststudies were carried out in the skeletal muscle. The increase in MMP activity is an early and critical featureof angiogenesis in skeletal muscle when initiated by mechanical stimuli which lead to breakage of the basementmembrane but not by stimuli such as shear stress that act via the luminal surface of vessels. AlthoughMMPs seem to play a important role in sprouting angiogenesis induced by exercise, in our knowledge theirfunction in exercised hearts has not been still tested. It is known that elevated levels of tissue inhibitors ofthe MMPs (TIMPs) may contribute to the accumulation of collagen content in the infarcted heart leading tomyocardial fibrosis. Therefore, a positive modulation of MMP system by exercise in heart failure-relatedmyocardial remodelling could lead to a ECM with a less fibrous component and more angiogenic sproutingin order to preserve the cardiac function.
Lingua originaleEnglish
Titolo della pubblicazione ospiteExperimental Medicine Reviews Morphophysiological Remarks
Pagine81-90
Numero di pagine10
Stato di pubblicazionePublished - 2008

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