Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 40, Issue 1, Pages 34-44Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.119.312863
Keywords
bone marrow; humans; ischemia; regeneration; stem cells
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Funding
- British Heart Foundation [RJ5905]
- Italian Ministry of Health Ricerca Corrente
- Cariplo Foundation [Rif 2016-0922]
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Diabetes mellitus increases the risk and accelerates the course of peripheral artery disease, making patients more susceptible to ischemic events and infections and delaying tissue healing. Current understanding of pathogenic mechanisms is mainly based on the negative influence of diabetes mellitus on atherosclerotic disease and inflammation. In recent years, the novel concept that diabetes mellitus can impinge on endogenous regenerative processes has been introduced. Diabetes mellitus affects regeneration at the local level, disturbing proper angiogenesis, collateral artery formation, and muscle repair. Recent evidence indicates that an impairment in vascular mural cells, alias pericytes, may participate in diabetic peripheral vasculopathy. Moreover, the bone marrow undergoes a global remodeling, consisting of microvessels and sensory neurons rarefaction and fat accumulation, which creates a hostile microenvironment for resident stem cells. Bone marrow remodeling is also responsible for detrimental systemic effects. In particular, the aid of reparative cells from the bone marrow is compromised: these elements are released in an improper manner and become harmful vectors of inflammatory and antiangiogenic molecules and noncoding RNAs. This new understanding of impaired regeneration is inspiring new therapeutic options for the treatment of ischemic complications in people with diabetes mellitus.
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