Cardiovascular Research Advance Access [Accepted Manuscript] published online on February 15, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn039
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Diabetes and Vessel Wall Remodeling: from Mechanistic Insights to Regenerative Therapies
* Bristol Heart Institute, University of Bristol, Bristol, UK
IRCCS Multimedica, Milan, Italy
Corresponding author: Paolo Madeddu, MD, CS, FAHA Chair Experimental Cardiovascular Medicine Bristol Heart Institute, University of Bristol, Upper Maudlin Street, Bristol, BS2 8HW, UK Email: madeddu{at}yahoo.com Tel/Fax: 0044 117 9283904
Over the past two decades, extensive research has focused on arterial remodeling in both physiological and pathological aging. The concept now describes the growth as well as the rearrangement of cellular components and extracellular matrix, resulting in either reduction or increase in vessel lumen. In diabetes, remodeling extends to capillaries, microvascular beds, and arteries of different caliber. This process is paralleled by accelerated atherosclerosis and accounts for an increased incidence of ischemic complications. The incapacity of pre-existing and de novo formed collaterals to bypass atherosclerotic occlusions, combined with a decline in tissue capillary density, is responsible for the delayed recovery from ischemia and ultimately leads to organ failure. The mechanisms of vascular remodeling are incompletely understood, but metabolic and mechanical factors seem to play an important role. Hyperglycemia represents the main factor responsible for the fast progression of atherosclerosis as well as microangiopathy. However, intensive blood glucose control alone is insufficient to reduce the risk of macrovascular complications. Pharmacological control of oxidative stress and stimulation of nitric oxide release have proved to exert beneficial effects on vascular remodeling in experimental diabetic models. New approaches of regenerative medicine using vascular progenitor cells for the treatment of ischemic disease have been shown to be safe and are now being tested for efficacy in pre-clinical and clinical trials.
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