Diabetes and vessel wall remodelling: from mechanistic insights to regenerative therapies

IRCCS Multimedica, Milan, Italy.
Cardiovascular Research (Impact Factor: 5.81). 06/2008; 78(2):265-73. DOI: 10.1093/cvr/cvn039
Source: PubMed

ABSTRACT Over the past two decades, extensive research has focused on arterial remodelling in both physiological and pathological ageing. 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, remodelling extends to capillaries, microvascular beds, and arteries of different calibre. This process is paralleled by accelerated atherosclerosis and accounts for an increased incidence of ischaemic 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 ischaemia and ultimately leads to organ failure. The mechanisms of vascular remodelling are incompletely understood, but metabolic and mechanical factors seem to play an important role. Hyperglycaemia 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 remodelling in experimental diabetic models. New approaches of regenerative medicine using vascular progenitor cells for the treatment of ischaemic disease have been shown to be safe and are now being tested for efficacy in pre-clinical and clinical trials.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Diabetes mellitus is the most common metabolic disorder and is recognized as a dominant health threat of our time. Diabetes induces a widespread damage of the macro and microvasculature in different organs and tissues and disrupts the endogenous vascular repair mechanisms, thus causing diffuse and severe complications. Moreover, diabetic patients respond poorly to surgical interventions aiming to "revascularize" (i.e, to restore blood flow supply) the ischemic myocardium or lower limbs. The molecular causes underpinning diabetes vascular complications are still underappreciated and druggable molecular targets for therapeutic interventions have not yet clearly emerged. Moreover, diabetes itself and diabetes complications are often silent killers, requiring new prognostic, diagnostic and predictive biomarkers for use in the clinical practice. Non-coding RNA (ncRNAs) are emerging as new fundamental regulators of gene expression. The small microRNAs (miRNAs, miRs) have opened the field capturing the attention of basic and clinical scientists for their potential to become new therapeutic targets and clinical biomarkers. More recently, long ncRNAs (lncRNAs) have started to be actively investigated, leading to first exciting reports, which further suggest their important and yet largely unexplored contribution to vascular physiology and disease. This review introduces the different ncRNA types and focuses at the ncRNA roles in diabetes vascular complications. Furthermore, we discuss the potential value of ncRNAs as clinical biomarkers and we examine the possibilities for therapeutic intervention targeting ncRNs in diabetes. This article is part of a Special Issue entitled SI: Non-coding RNAs. Copyright © 2014. Published by Elsevier Ltd.
    Journal of Molecular and Cellular Cardiology 12/2014; DOI:10.1016/j.yjmcc.2014.12.014 · 5.15 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Emergency treatment options in myocardial infarction are guided by presence or absence of ST-elevations in electrocardiography. Occurrence and factors associated with ST-presentation in different population groups are however inadequately known.
    PLoS ONE 09/2014; 9(9):e108440. DOI:10.1371/journal.pone.0108440 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Structural and functional change in the microcirculation in type 1 diabetes mellitus predicts future end-organ damage and macrovascular events. We explored the utility of novel signal processing techniques to detect and track change in ocular hemodynamics in patients with this disease. 24 patients with uncomplicated type 1 diabetes mellitus, and 18 age-and-sex matched control subjects were studied. Doppler ultrasound was used to interrogate the carotid and ophthalmic arteries and digital photography to image the retinal vasculature. Frequency analysis algorithms were applied to quantify velocity waveform structure and retinal photographic data at baseline and following inhalation of 100% oxygen. Frequency data was compared between groups. No significant differences were found in the resistive index between groups at baseline or following inhaled oxygen. Frequency analysis of the Doppler flow velocity waveforms identified significant differences in bands 3-7 between patients and controls in data captured from the ophthalmic artery (p<0.01 for each band). In response to inhaled oxygen, changes in the frequency band amplitudes were significantly greater in control subjects compared with patients (p<0.05). Only control subjects demonstrated a positive correlation (R=0.61) between change in retinal vessel diameter and frequency band amplitudes derived from ophthalmic artery waveform data. The use of multimodal signal processing techniques applied to Doppler flow velocity waveforms and retinal photographic data identified preclinical change in the ocular microcirculation in patients with uncomplicated diabetes mellitus. An impaired autoregulatory response of the retinal microvasculature may contribute to the future development of retinopathy in such patients.
    AJP Heart and Circulatory Physiology 10/2014; DOI:10.1152/ajpheart.00372.2014 · 4.01 Impact Factor

Full-text (2 Sources)

Available from
Jun 4, 2014