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Patrolling Monocytes Are Recruited and Activated by Diabetes to Protect Retinal Microvessels.
- Source :
-
Diabetes [Diabetes] 2020 Dec; Vol. 69 (12), pp. 2709-2719. Date of Electronic Publication: 2020 Sep 09. - Publication Year :
- 2020
-
Abstract
- In diabetes there is a long latency between the onset of hyperglycemia and the appearance of structural microangiopathy. Because Ly6C <superscript>low</superscript> patrolling monocytes (PMo) behave as housekeepers of the vasculature, we tested whether PMo protect microvessels against diabetes. We found that in wild-type mice, diabetes reduced PMo in the general circulation but increased by fourfold the absolute number of PMo adherent to retinal vessels (leukostasis). Conversely, in diabetic NR4A1 <superscript>-/-</superscript> mice, a model of absence of PMo, there was no increase in leukostasis, and at 6 months of diabetes, the number of retinal acellular capillaries almost doubled compared with diabetic wild-type mice. Circulating PMo showed gene expression changes indicative of enhanced migratory, vasculoprotective, and housekeeping activities, as well as profound suppression of genes related to inflammation and apoptosis. Promigratory CXCR4 was no longer upregulated at longer duration when retinal acellular capillaries begin to increase. Thus, after a short diabetes duration, PMo are the cells preferentially recruited to the retinal vessels and protect vessels from diabetic damage. These observations support the need for reinterpretation of the functional meaning of leukostasis in diabetes and document within the natural history of diabetic retinopathy processes of protection and repair that can provide novel paradigms for prevention.<br /> (© 2020 by the American Diabetes Association.)
- Subjects :
- Animals
Gene Expression Regulation physiology
Mice
Mice, Knockout
Nuclear Receptor Subfamily 4, Group A, Member 1 genetics
Nuclear Receptor Subfamily 4, Group A, Member 1 metabolism
Diabetes Mellitus, Experimental complications
Diabetic Retinopathy metabolism
Monocytes physiology
Retinal Vessels pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1939-327X
- Volume :
- 69
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 32907815
- Full Text :
- https://doi.org/10.2337/db19-1043