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Review
. 2017 Aug 31;15(1):185.
doi: 10.1186/s12967-017-1280-y.

Multiple therapeutic effect of endothelial progenitor cell regulated by drugs in diabetes and diabetes related disorder

Rashmi K Ambasta  1 , Harleen Kohli  2 , Pravir Kumar  2
Affiliations
Review

Multiple therapeutic effect of endothelial progenitor cell regulated by drugs in diabetes and diabetes related disorder

Rashmi K Ambasta et al. J Transl Med. .

Abstract

Background: Reduced levels of endothelial progenitor cells (EPCs) counts have been reported in diabetic mellitus (DM) patients and other diabetes-related disorder. EPCs are a circulating, bone marrow-derived cell population that appears to participate in vasculogenesis, angiogenesis and damage repair. These EPC may revert the damage caused in diabetic condition. We aim to identify several existing drugs and signaling molecule, which could alleviate or improve the diabetes condition via mobilizing and increasing EPC number as well as function.

Main body: Accumulated evidence suggests that dysregulation of EPC phenotype and function may be attributed to several signaling molecules and cytokines in DM patients. Hyperglycemia alone, through the overproduction of reactive oxygen species (ROS) via eNOS and NOX, can induce changes in gene expression and cellular behavior in diabetes. Furthermore, reports suggest that EPC telomere shortening via increased oxidative DNA damage may play an important role in the pathogenesis of coronary artery disease in diabetic patients. In this review, different type of EPC derived from different sources has been discussed along with cell-surface marker. The reduced number and immobilized EPC in diabetic condition have been mobilized for the therapeutic purpose via use of existing, and novel drugs have been discussed. Hence, evidence list of all types of drugs that have been reported to target the same pathway which affect EPC number and function in diabetes has been reviewed. Additionally, we highlight that proteins are critical in diabetes via polymorphism and inhibitor studies. Ultimately, a lucid pictorial explanation of diabetic and normal patient signaling pathways of the collected data have been presented in order to understand the complex signaling mystery underlying in the diseased and normal condition.

Conclusion: Finally, we conclude on eNOS-metformin-HSp90 signaling and its remedial effect for controlling the EPC to improve the diabetic condition for delaying diabetes-related complication. Altogether, the review gives a holistic overview about the elaborate therapeutic effect of EPC regulated by novel and existing drugs in diabetes and diabetes-related disorder.

Keywords: Diabetes; EPC; Metformin; NOX; ROS; eNOS.

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Figures

Fig. 1
Fig. 1
This schematic demonstrates healthy mobilization of EPC due to high cytokines, high p-Akt, high NO released by eNOS and low superoxide by NADPH oxidase
Fig. 2
Fig. 2
This schematic demonstrates defective mobilization of EPC and dysfunctional EPC due to high ROS (via eNOS and NADPH Oxidase) and high glucose in diabetes
Fig. 3
Fig. 3
eNOS docking site (333, 334, 335,354, 355, 356, 357, 360, 361, 362) and polymorphism found in diabetes and uncoupling site
Fig. 4
Fig. 4
Signalling pathway in normal and hyperglycemia patients. Diabetes can be corrected by metformin. The major target of metformin is highlighted in red i.e. Uncoupled eNOS, HSp90, GST, CDK2, neuraminidase
See this image and copyright information in PMC

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